Report to the Workers' Compensation Board on Stomach Cancer in Ontario Gold Miners
August, 1996

Occupational Disease Panel
ODP Report No. 16
Toronto, Ontario

Occupational Disease Panel

In 1985, the Ontario legislature established the Industrial Disease Standards Panel to investigate and identify diseases related to work. The Panel is independent of both the Ministry of Labour and the Workers' Compensation Board. At the end of each fiscal year the WCB reimburses the Ministry for the Panel's expenditures. In 1995, the name was changed to the Occupational Disease Panel (ODP).

The Panel's authority flows from section 95 of the Workers' Compensation Act and its functions are set out as follows:

95(8)

Decisions of the Panel are made by its members who represent labour, management, scientific, medical and community interests. Once the Panel makes a finding, the WCB is required to publish the Panel's report in the Ontario Gazette and solicit comments from interested parties. After considering the submissions the WCB Board of Directors decide if the Panel's recommendations are to be implemented, amended or rejected.

To assist with its work, the Panel has a small staff of researchers, analysts and support people. In addition to its own staff, the Panel relies heavily on the advice of outside experts in science, medicine and law, as well as input from parties of interest.

Additional copies of this publication are available by writing:

Occupational Disease Panel
69 Yonge Street, Suite 1004
Toronto, Ontario M5E 1K3
(416) 327-4156

Panel Membership

Panel Staff

TABLE OF CONTENTS

Letter of Transmittal
Panel Members
Panel Staff

Chapter 1. The Panel's investigation

a) ODP mandate and terms of reference
b) The issue and how it arose
c) The focus of the investigation
d) The investigative process
e) Submissions
f) Other Panel initiatives
g) Other jurisdictions

Chapter 2. The evidence

a) Background information about stomach cancer
b) Preliminary considerations
c) The questions

1) What is the evidence concerning stomach cancer mortality among non-gold miners worldwide and in Ontario?
i) International studies - non-goldmining
ii) Provincial studies - non-goldmining
iii) Conclusions

2) What is the evidence concerning stomach cancer mortality among goldminers worldwide and in Ontario?
i) International studies - goldmining
ii) Provincial studies - goldmining
iii) Discussion
iv) Conclusions

3) What is known about potential occupational causes of stomach cancer?
i) Dr. Stock's review
ii) Conclusions

4) Are any of these and other potential causes relevant in the Ontario gold mining environment?
i) Airborne dusts
a. Arsenic
b. Asbestos
c. Silica
d. Chromium
ii) Polycyclic aromatic hydrocarbons(PAHs)
a) Oil mist
b) Diesel emission
iii) Nitroso compounds
iv) Conclusions

5) What, if any, are the differences between gold mining and other kinds of hardrock mining in Ontario?
i) Backfill
ii) Aluminum powder
iii) Underground working environment
iv) Conclusions

6) Are there other risk factors that could affect the pattern of stomach cancer?
i) Diet
ii) Cigarette smoking and alcohol consumption
iii) Ethnicity and place of birth
iv) Conclusions

Chapter 3. Summary of conclusions

Chapter 4. The Bradford Hill criteria for a causal association

Chapter 5. Findings and recommendations

References

Appendix A: Summary of epidemiologic studies of gastric cancer and occupation

Appendix B: Report on analysis of stomach cancer among Ontario gold miners.

Figure 1.
The stomach

Figure 2.
Stomach cancer in non-gold mining (world)

Figure 3.
Stomach cancer in non-gold mining (Ontario)

Figure 4.
Gold mining and mixed gold mining

Figure 5.
Gold mining, Muller 1983, and stomach cancer

Figure 6.
(Post 1945 start) and stomach cancer mortality among Goldminers

Figure 7.
Stomach cancer and age at death

Figure 8.
Stomach cancer among gold miners and birthplace

Figure 9.
Fitted SMRs from Poisson regression

Figure 10.
Northern Ontario male population compared to all Ontario males

Figure 11.
Miners compared to the Northern Ontario male population

Figure 12.
Miners compared to all Ontario males

Figure 13.
Flow diagram of gold mining process

Table 1.
Summary of evidence of gold mining and stomach cancer mortality

For the purposes of this report, the Panel has adopted the following definitions:

Miner: refers to any person employed underground; in shaft sinking; and surface crushing; grinding; milling and tailings operations. All other surface work is excluded.

Goldminer: a miner with at least 85 % of mining time or 51 months in the foregoing employment whichever is less of which two weeks must have been in Ontario.

Stomach Cancer: means primary cancer of the stomach (International Classification of Diseases,7th, 8th & 9th Revisions, code#151).

CHAPTER 1. THE PANEL'S INVESTIGATION

a) The ODP mandate and terms of reference

The Occupational Disease Panel (ODP) is mandated by the legislation to investigate possible occupational diseases and, when appropriate, make findings of "probable connection" between disease and work (103).

The Panel's specific responsibilities are set out in section 95 of the Workers' Compensation Act which reads as follows:

95(8)

After weighing all of the evidence, the Panel decides whether or not a probable connection exists between occupation and disease. If the results of the investigation do not indicate the existence of an association, the Panel will also report those findings.

When a probable connection is identified, depending on its strength, the Panel may recommend that the Workers' Compensation Board (WCB) enact guidelines for adjudication of claims on a case-by-case basis, or it may recommend that the disease and the relevant exposure(s) be added to Schedule 3 or 4 of the Act.

When a worker suffers from one of the diseases listed in the "Disease" column of Schedule 3 and can show that he or she was exposed to the associated substance or industrial process shown in the "Process" column, the Act states that the disease "shall be deemed to have been due to the nature of that employment unless the contrary is proved".

A Schedule 4 presumption, however, is termed "irrebuttable". Created by 1984 amendments to the Act, this presumption is only used in cases where the evidence of a work-relationship is indisputable. At present, only asbestosis, mesothelioma and cancer of the nasal cavities or paranasal sinuses are in Schedule 4. This means, for example, that if a worker has worked in a process involving asbestos listed in Column 2 and has a diagnosis of either mesothelioma or asbestosis, the disease is presumed caused by work and benefits are automatic without further investigation.

Readers are welcome to contact the ODP at (416) 327-4156 to receive more detailed information about these decision-making principles used by the Panel.

b) The issue and how it arose

In 1983, Dr. Jan Muller et al. of the Ministry of Labour, published a report entitled "Study of Mortality of Ontario Miners, 1955-1977, Part I" sponsored jointly by the Ontario WCB and the Atomic Energy Control Board of Canada. Although focusing primarily on lung cancer, some analysis was done on stomach cancer. The authors found a statistically significant 48% increase in stomach cancer among underground goldminers (61).

In 1984, Muller and colleagues described the results from an extension of the follow-up of their cohort of uranium miners through 1981. This study found an excess of stomach cancer among uranium miners who had prior gold experience compared to the no gold portion of the cohort (62). This finding was later confirmed in 1989 in an updated report (65).

In 1986, in conjunction with colleagues from the WCB and the University of Toronto, Dr. Muller provided Part II of the earlier study, taking a more detailed look at the excess of stomach cancer. Their new analysis found that goldminers experienced a 57% increase in stomach cancer (63). In response to queries from the WCB and others, an explanatory Addendum was also published in 1987 (64).

These findings prompted the United Steelworkers of America (USWA) in 1986 to request that the government authorize compensation of the victims' families from the WCB, in the belief that the cancers were work-related (81). When the Steelworkers made their request the ODP had just been created and was not yet functioning. For that reason the WCB decided to undertake an investigation of its own and asked Dr. A. B. Miller and his colleagues at the University of Toronto to investigate the pattern of lung and stomach cancer among Ontario goldminers. The Miller mandate was to evaluate the questions originally posed to the ODP.

In a letter dated August 18, 1986, the WCB had requested the ODP⁽¹⁾ to respond to a number of questions about the occurrence of lung and stomach cancer among goldminers (53). Regarding stomach cancer specifically, the Board asked:

"Does there exist sufficient evidence for the WCB to provide compensation benefits to gold or mixed ore miners who have subsequently contracted stomach cancer? If the answer to the [above] question is yes, then what criteria should the Board employ to compensate this category of workers?"

The Panel began an investigation to answer the Board's questions and struck a special scientific sub-panel, chaired by Dr. Harry Shannon to conduct an epidemiological review of the lung and stomach cancer mortality experience of various mining cohorts in Ontario. Both Dr. Miller and Dr. Shannon employed data from the Mining Master File (MMF) as had Dr. Muller.

The ODP reported the results of both scientific investigations. Dr. Miller found a 36% increase in stomach cancer among goldminers. While this increase in incidence of stomach cancer could represent an occupational role in disease, Miller suggested reasons for scepticism: no dose-response relationship; mixed ore miners showed no increased risk of stomach cancer; and few other studies of goldminers showed an increase in mortality from stomach cancer (57).

Shannon assembled a cohort which was larger and included more multi-ore miners than the Miller study. The Shannon sub-panel reported an overall stomach cancer excess of 42% among goldminers. Similar to Miller's study the highest standardized mortality ratio (SMR) was found for those with first exposure after 1950 (83).

In April 1987, based on the findings of these two studies the IDSP issued the final report to the WCB, (36). In that Report , it concluded that at best, the relationship between stomach cancer and gold mining was considered inconclusive. The Panel stated its intention "to review the evidence when the Muller report is updated and requests that as full as possible an update be carried out as soon as possible".

In its submission to the WCB following release of the IDSP report, the USWA suggested that the causative agent for stomach cancer for those miners who worked after 1945 might be found in the mixture of new chemical agents such as aluminum dust, blasting agents and diesel fumes (95).

The topic of stomach cancer and goldminers re-appeared on the ODP agenda when a further study was published in 1993. Kusiak et al. reported a 52% excess of stomach cancer among Ontario goldminers(44). This last study initiated the current investigation by the Panel.

c) The focus of the investigation

To answer the questions originally posed by the WCB in 1986, the Panel asked itself the following:

1. What is the evidence concerning stomach cancer mortality among non-gold miners worldwide and in Ontario?

2. What is the evidence concerning stomach cancer mortality among goldminers worldwide and in Ontario?

3. What is known about potential occupational causes of stomach cancer?

4. Are any of these and other potential causes relevant in the Ontario gold mining environment?

5. What, if any, are the differences between gold mining and other kinds of hardrock mining in Ontario?

6. Are there other risk factors that could affect the pattern of stomach cancer?

d) The investigative process

As the first step in its most recent investigation the ODP commissioned Dr. Susan Stock, Medical Consultant, Occupational and Environmental Health Unit of the Montreal Department of Public Health, to conduct a review of the world literature relating stomach cancer and occupation. That paper, entitled Gastric Cancer and Occupation: A Review of the Literature (1993), was reviewed by Dr.J.M. Peters (78), Dr. M. Neuberger (71) and Drs. M. Isler and M. Caron (39). Dr. Stock revised her work in accordance with the comments in 1994 (87). Appendix A of this report sets out the studies she evaluated together with her references.

e) Submissions

Following the review the Panel made copies available to interested stakeholders. Notice of the Panel's investigation was published in August 1993 in the Ontario Gazette. The following chose to comment:

• Ka Sing Yeung, Epidemiologist
  Workers' Compensation Board
• J.Stuart Warner, Vice President
  INCO Limited
• Bruce Campbell, Manager, Technical Service
  Ontario Mining Association

f) Other Panel Initiatives

• In late 1994, ODP staff visited Northern Ontario gold mines. The trip was designed to investigate the possible differences between the gold mining process and other mining processes in Ontario.
• The Panel also had samples of water used in Ontario gold mines analyzed by the Ministry of Environment and Energy.
• Throughout its work on this issue, the Panel was assisted by the staff of the Ministry of Labour Health and Safety Studies Unit and the ODP biostatistician in additional analyses of the MMF.

g) Other Jurisdictions

British Columbia, Manitoba, Newfoundland, Saskatchewan and Ontario have policies dealing with stomach and/or gastrointestinal cancer with a clear history of exposure to asbestos.

Alberta, New Brunswick, Northwest Territories, Nova Scotia, Prince Edward Island, Quebec and the Yukon adjudicate such claims on their individual merits with no specific policies in place.

The Ontario Board reports that it has received claims for stomach cancer from gold miners, but that none have been allowed due to gold mining.(50)

CHAPTER 2. THE EVIDENCE

a) Background information about stomach cancer

Stomach cancer: what is known in general

• mortality from stomach cancer declined by 90% in industrialized nations over the past 60 years (25 to approximately 6 per 100,000) (86,27),
• occurs in North America at a mean age of 60 with less than 5% under age 40 (27),
• has a regional, age-standardized incidence variance across Canada: lowest in B.C. at 10/100,000 population and highest in Newfoundland at 23/100,000 - Canadian average is 13/100,000 and Ontario is 14/100,000 (68),
• is almost twice as common in Ontario men as Ontario women(68)

  age-standardized incidence rates/100,000 for Ontario males between 1989-1991 ranged as follows:
  Ages 15-34 (0.05); ages 35-54 (2.80); ages 55-74 (23.85); ages 75+ (41.41) (75)

• mortality from 1974-86 was 27% higher in Northern Ontario men than men in Ontario in general (74). Rates in Northern Ontario women in the same counties are elevated by 15%.

Types of gastric cancers

Please refer to Figure 1 for the structure of the human stomach.

Approximately 85-90% of gastric cancers are gland like malignant tumours (adenocarcinomas), and according to the Lauren Classification based on histology, they are divided into two types: intestinal or diffuse (47).

Intestinal types are marked by cohesive abnormal cells forming gland like tubular structures, believed to have a long pre-cancerous process. Most ulcerating tumours fall into this category, and these tumours occur most often in the antrum. The intestinal type is more common in men and patients over 60 years of age, and appears to be more affected by diet/environmental factors than the diffuse type. The intestinal type is also

associated with a pre-cancerous stage of gastric atrophy and metaplasia⁽²⁾ (28).

Diffuse types lack cell cohesion. These predominate in younger patients and develop throughout the stomach (including cardia), resulting in a "leather-bottle appearance", with a far more ominous prognosis (86). The incidence of diffuse gastric carcinoma appears to be similar in most populations worldwide (52).

b) Preliminary considerations

In the following pages we will discuss the mortality from stomach cancer among miners.

The following explanation of Standard Mortality Ratios may assist the reader:

"Standardized Mortality Ratios" (SMR)

Results are measured in terms of a "standardized mortality ratio" ("SMR"), which is an estimate computed by comparing the number of deaths observed among miners with the number of deaths which are expected based upon a comparison group of the same age and sex, during the same time period (then multiplying by 100):

                  "observed" deaths among miners         
SMR =   ------------------------------------------------ X 100
             "expected" deaths among comparison group  

For example, if among 1000 miners three died of stomach cancer, whereas two of 1000 individuals in the comparison group of the same age and sex died of stomach cancer:

         (observed) 3		    
SMR is -----------------   X 100 = 150.
          (expected) 

An SMR greater than 100 would suggest an excess risk of stomach cancer. Epidemiologists evaluate the statistical significance of an SMR by using a 95% confidence interval, a range of numbers in which the true SMR would fall 95% of the time. If the lower end of the 95% confidence interval is above 100, the likelihood that the excess mortality is due to chance is less than 5% (or 1 out of 20). In this Report, confidence intervals, where available from the original paper, are noted. When not available, they were calculated using the following formula:

Lower limit = [Square root of Observed events - (1.96 x 0.5)]2
              ------------------------------------------------
                                 Expected

Upper limit = [Square root of Observed events + (1.96 x 0.5)]2
              ------------------------------------------------
                                 Expected

It is also important to note that the SMRs may not accurately reflect the excess mortality or true risk for the following reasons:

Healthy worker effect

Most epidemiological studies compare workers with the general population. Since the general population includes people who do not or cannot work due to illness or disability, a working population is usually healthier and is, therefore, expected to have a lower mortality rate for most causes of death. The influence of these factors on the results of studies is known as the "healthy worker effect". It results in lower SMRs than would occur if more similar groups had been compared and may conceal a real increase in deaths among workers. In other words, the phenomenon results in an underestimation of the excess caused by work exposures. Comparisons with another group of "healthy" workers, rather than to the general population, are therefore more likely to provide accurate statistical estimates of occupational risks.

Whether or not the healthy worker effect influences cancer mortality ratios is controversial. In a previous Report of Findings [HWE report], the IDSP published comments on the healthy worker effect solicited from nine experts. The Panel's review of those opinions led it to conclude that the healthy worker effect must be taken into account when interpreting epidemiological studies of mortality or morbidity from any cause, including cancer.

Accuracy of the data

Because epidemiological cohort studies follow subjects over a long period of time many people may be difficult to trace. A portion of these subjects may die outside Canada and their deaths would not be accurately recorded.

The ODP has concluded that the SMR for stomach cancer has been underestimated in all of the studies of Ontario miners primarily because of the lack of social insurance numbers (SINs) to accurately ascertain mortality. In fact, the vital status of 25% of all miners without SINs could not be determined, compared to the ascertainment of the vital status of all but 5% of those miners with SINs (45).

Estimating the extent of disease when comparing working populations to the general population

When the SMR is computed, the general population, on which the expected number of deaths is based, includes the observed number of deaths from the study population. This is because these deaths contribute to both populations: i.e., the deaths are counted in both the observed and the expected, thus underestimating the real excess. If deaths from a disease such as nasal cancer are caused almost always by occupational factors, the SMR will thus be even more underestimated.

The preceding factors constitute the framework within which reports of SMRs need to be considered. The following account of the SMRs found in mining cohort studies are affected by questions of data accuracy, the healthy worker effect and population comparisons. They should be evaluated with these factors taken into account.

c) The questions

1) What is the evidence concerning stomach cancer mortality among non-gold miners worldwide and in Ontario?

i) International studies - Non-gold Mining

Figures 2 and 3 on the following pages show the SMRs from studies of stomach cancer among non-goldminers worldwide and in Ontario respectively.⁽³⁾

Statistically significant elevated stomach cancer rates were found in copper mining in China (13,15) and iron ore in the U.S. and France (48,79).

Although not statistically significant, excesses were found likewise in tin miners in the U.K (22,30), iron ore miners in the U.K.(42) and France(12); and uranium miners in the U.S.(97), N.W.T. and Saskatchewan(67), and Newfoundland (59).

Four studies, two among mixed ore miners in Italy (11,14) and two among iron ore miners in China and France (14,66) do not show increases in stomach cancer mortality.

It should be noted that although there are a large number of studies on stomach cancer among coal miners, they are not reviewed here but are referred to later in other sections of the text. Such studies also formed part of the review on the worldwide literature conducted by Dr. Stock.

ii) Provincial studies - Non-gold Mining

In Ontario the rates of stomach cancer among all miners including gold, nickel, uranium and mixed miners have been considered by Muller and Kusiak during three different periods of follow-up: 1955-77; 1955-1981 and 1955-86.

In 1983 Muller et al. reported an SMR of 108 for nickel/copper miners (61)

and in 1993 Kusiak et al. found an SMR of 101 (44). Uranium miners, other ore and mixed ore but non-goldminers likewise showed no statistically significant increase. The 1985 study by Nair et al. was on refinery workers extracting radium from uranium ore and who overall exhibited a strong healthy worker effect (67).

iii) Conclusions

As cited in Figure 2, the evidence of an increase in the rates of stomach cancer among non-gold miners worldwide is inconsistent. However, the literature supports the potential work-relatedness of stomach cancer among certain occupational groups as described in the review by Susan Stock (87).

There is no evidence of a statistically significant increase in stomach cancer mortality among non-goldminers in Ontario.

2. What is the evidence concerning stomach cancer mortality among goldminers worldwide and in Ontario?

i) International studies - Gold Mining

There are three studies of non-Ontario cohorts which examine the mortality from stomach cancer among goldminers; two of these studies show elevated rates. Wyndham reports an elevated but non-statistically significant excess of stomach cancer (SMR 157, CI 78-281) when white South African goldminers were compared to the white South African male population (107). In a study of Russian workers who were exposed to non-fibrous mineral dusts, Katsnelson and Mokronosova reported a relative risk (RR) 5.7 for stomach cancer for miners working in gold mines (41). The only cohort which did not show an excess was a study conducted of the goldminers in South Dakota (8). The SMR for that cohort was 57. This unusual finding is in keeping with the unique experience in South Dakota which also reports lower than expected SMRs for lung cancer, in contrast to most other studies of goldminers.

Figure 4, on the next page, illustrates the mortality experience of underground goldminers worldwide, including Ontario. More detailed information on the cohorts follows on Table 1. (Although other studies exist, the Panel has routinely excluded studies which report fewer than five deaths for the cause of interest and that practice has been adopted here, except for the sub-comparisons among gold mining camps within Ontario).

ii) Provincial studies - Gold Mining

All of the studies of Ontario goldminers confirm elevated rates of stomach cancer. The five analyses of the Ontario cohort (Muller et al., 1983; Muller et al.,1986; Shannon 1987; Miller 1987; and Kusiak et al.,1993) used the same gold mining cohort with modifications and different follow-up durations from the MMF maintained by the Ministry of Labour. For the various studies the cohort has been described as follows:

Muller et al, 1983, defined a goldminer as a miner who (a)spent at least 60 months in non-uranium mines, of which 85% was in gold with a minimum of two weeks in an Ontario mine (b)was alive between January 1, 1955 and December 31, 1977 and (c)underwent a chest x-ray each year as required for a mining

TABLE 1: SUMMARY OF EVIDENCE OF GOLD MINING AND STOMACH CANCER MORTALITY

AUTHOR(S): YEAR	NUMBER OF SUBJECTS	YEARS STUDIED	COMPARISON CONTROL GROUP	GEOGRAPHICAL LOCATION	"CAUSAL" FACTORS?	DEFINITION GOLD MINER	SMR (95% C.I.) O/E	COMMENTS
Muller et al (1983)	7,542	1955-77 (23 years)	Ontario males	N. Ontario	-	-non-uranium, 5 yrs mining, 2 weeks Ont mine 85% gold mining by 1977, at death, or becoming uranium miner -annual chest x-ray after 1954 -underground and dusty surface jobs	148 (113-188) 60/40.4 - Ont. 148 (103-205)-35/23.7-Timmins 121 (63-211)-12/9.9-Kirkland Lake Ft. William Renabie	-highest mortality <50 years old (SMR=393, 9/2.3)
Muller et al (1986, 1987)	7.057	1955-77 (23 years)	Ontario males nickel/copper	N. Ontario	-	-non-uranium, 5yrs+ mining, 2 weeks + Ont mine, 85% gold mining by 1977, at death or becoming uranium miner -annual chest x-ray -must be employed anytime 1955-1977 2 weeks -FT if 50% underground -underground and dusty surface jobs	157 (118-121) 54/34.3 154 - born in Canada 136 - born outside Canada 238 (no CI available)	-immigrant status not a satisfactory explanation of excess
Wyndham et al (1986)	3.971 white males	1970-79 (10 years)	white S. African males	S. Africa	-miner's lifestyle (diet, smoking, alcohol)	-born between 1916-1930 and alive 1970 -followed for nine years	157 (78-281) 11/7	-rejects healthy worker effect -miners lifestyle less healthy than pop.? -too labourious to collect smoking histories -no arsenic found in certain mines -dust level index counted
Brown et al (1986)	3,328 white males	1940-65 (26 years)	S. Dakota State males	S. Dakota, U.S.	-arsenic (to 1952) confounding effects from amphibole fibres or silica	-FT underground at least 1 year, 1940-65 -non-uranium exposure	57 (18-133) 5/8.8	-rates possibly underestimated due to standard pop. used -smoking prohibited in mines until 1952 -negligible trace metal quantities in air -dust level index exposure created -reduced dust exposure underground due to reduced working hours from 1920 to 1986
Miller et al (1987) retrospective mortality cohort	7,057	1955-77 (23 years)	Ontario males	N. Ontario	-ethnicity	-5 yrs. + gold mining, 2 weeks + Ont. gold mine between 1955-77 -underground & dusty surface jobs -mixed ore & gold (non-uranium) -annual chest x-ray -85% gold	136 (105-171) 66/48.5 113 (81-145) <1945 221 (159-283) >1945	-cigarette smoking weak factor -healthy worker effect? -low colo-rectal mortality -heaviest dust <1945
Kusiak et al (1993)	11,097 ever gold never uranium never gold	1955-87 (33 years)	Ontario males	N. Ontario	-metal dust -chromium	-5 yrs + mining after 1954 -2 weeks +, Ont. mining -annual chest x-ray -85% gold	152(125-185) 104/68.2 160 (115-218) 41/25.6 -born outside N. America 102 (88-128)	-no increase for non-gold miners -rejects arsenic, diesel emissions, mineral fibre, aluminum powder -5-19 yrs latency -no dietary confounders considered -excess greater in <60 age group -weighting to dust -<60 intestinal rather than diffuse gastric cancer -no direct exposure measurement -best fit to dates chromium and/or dust
Shannon et al (1987)	10,185 ever gold 6,786 pure gold	1955-77 (23 years)	Ontario males N.Ontario males	N. Ontario	-labour intensive efforts as indicated by job	-5 yrs+ gold mining -underground & dusty surface jobs -2 weeks + Ont gold, between 1955-77 -mixed ore & gold (non-uranium)	142 (109-180) 63(44.4) 114 (88-146) 63 (55.3) N. Ont.	-10-19 yrs latency -inverse dose response -excess higher for native born Canadian/US -quantifying exposure and levels of contamination not available -reduced dust over time and varied mine to mine
Katsnelson et al (1979)		1948-74 (27 years)	-corresponding town in Russia males	Russia	-silica -PAH in tobacco smoke -nonfibrous industrial dust	-underground and surface broken into occupational groups	RR=5.7 underground RR=1.1 surface RR=4.4 underground minus silicosis persons

certificate(61).

Muller et al.,1986, restricted the cohort to require that an individual had to actually be working in a gold mine(i.e. not retired from gold mining) when reporting for his annual chest x-ray (63).

Shannon specified 60+ months as a goldminer with a minimum of two weeks in an Ontario gold mine (83), while Miller 1987 (57) used Muller's 1986 cohort definition.

Kusiak et al., 1993, broadened the cohort by dropping the 85% rule and defined a goldminer as someone who has ever worked in a gold mine but has spent 60 months (five years) or more as a non-uranium miner, with two weeks or more in an Ontario mine, as well as having an annual chest x-ray taken (44). This definition could therefore include mixed ore mining, and underground and dusty surface jobs.

The overall rates of stomach cancer have been identified as follows:

Gold Mining and Stomach Cancer

1993 Kusiak (Ont)	n=104	SMR 152	CI 125-185
1987 Miller (Ont)	n=66	SMR 136	CI 105-171
1987 Shannon (Ont)	n=63	SMR 142	CI 109-180
1986 Muller (Ont)	n=54	SMR 157	CI 118-202
1983 Muller (Ont)	n=60	SMR 148	CI 113-188

As part of his analysis Shannon compared the goldminers to the general Ontario male population and also to the Northern Ontario male population The SMR for stomach cancer was reduced from 142 to 114 (not statistically significant) when the Northern Ontario population was used as the control group. ODP staff conducted a person-years analysis and confirmed that the stomach cancer deaths among the gold miners formed less than five percent of the total number of deaths from stomach cancer in Northern Ontario counties (89). Thus there was little bias caused by including mining-exposed deaths in the Northern Ontario reference rates. However, Muller et al., 1986, had compared the goldminers to what was perhaps the most ideal control group, the nickel/copper miners. In this comparison, Muller found that the SMR for the goldminers was a statistically significant 238 in those under the age of 70. Kusiak et al., 1993, also observed that although empirically,

" mortality from stomach cancer for gold miners ought to have been compared with that of men living in Northern Ontario......many of the men in Northern Ontario worked in the mines and no excess gastric carcinoma relative to the male population in the whole of Ontario was evident in northern Ontario miners who mined nickel and copper or uranium only."

Figure 5 reflects the efforts of Muller et al., in their seminal 1983 study, to search for any differences in mortality between gold camps which were located as much as 500 miles apart. In all gold camps, an excess of stomach cancer mortality was found, although not always reaching statistical significance because of small numbers. However when placed in one gold cohort, statistical significance is achieved.

In addition to the research chiefly focused on the variously defined gold mining cohorts, other evidence produced concurrently or as off-shoots of other studies needs to be considered.

Muller et al., 1983 found excess stomach cancer among mixed ore miners only if their mining experience had included gold. In mixed camps with no gold, there was no excess (Fig.3). In 1984, Muller et al. extended the follow-up period for uranium miners in their original cohort from 1977 to 1981. They found an excess of stomach cancer (SMR=157, CI 84-268) only among uranium miners who had also mined gold. This finding was confirmed in 1989 as a statistically significant excess (SMR =196, CI 118-306) again only among uranium/goldminers. This evidence is shown in Figure 4 as mixed gold mining. In both cases the uranium only miners showed no excess with SMRs of 94 and 95, respectively.

In an unrelated but relevant study, also shown in Figure 4, Finkelstein et al.,1987 (20) found a statistically significant excess of stomach cancer among compensated silicotic miners (SMR=188, CI 120-290). It can be reasonably assumed that the vast majority of these miners were goldminers because they received compensation for silicosis before 1970. The only other miners likely to have developed silicosis are uranium miners who, in most cases, would have had insufficient exposure prior to 1970 to have qualified for workers' compensation benefits.

PARTICULAR ASPECTS OF THE ONTARIO DATA

Calendar date of first employment

Excesses of stomach cancer are found in all time periods studied. The highest SMRs are observed among gold miners first hired after 1945. Most authors, excluding Kusiak et al., provided findings for those workers who commenced employment pre and post 1945 (Shannon,1987; Muller et al.,1987; Miller,1987).⁽⁴⁾

In addition, Shannon grouped those men first exposed from 1950 onwards and found that they had the highest SMR (SMR=330, CI 178-570).

The findings are shown in the table below and illustrated in Figure 6.

Year of First Employment (Post-1945 Start) and Stomach Cancer Mortality

Miller et al., 1987	n=19	SMR 322	CI 240-405
Shannon et al., 1987	n=22	SMR 286	CI 179-418
Muller et al., 1987	n=19	SMR 322	CI 194-483

Age

The 1987 studies of Muller et al., Shannon et al., and Miller et al. all observed that younger goldminers are more at risk of stomach cancer than older ones.

Muller et al. found the highest SMRs among the goldminers in those under the age of 50 (SMR 393, CI 180-746). The risk decreased with age.

Regression analysis found that the effect of age was statistically significant.

Miller et al., looking at age at death among gold and mixed ore miners with stomach cancer, found a statistically significant increase only among

those miners employed in 1945 or later and under the age of 50. For reasons that are explained beginning on Page 33 of this report, Miller's results are displayed in Figure 7 without regard for period of hire.

The 1993 study of Kusiak et al. confirmed these earlier findings. The excess of stomach cancer was higher in gold miners under the age of 60 (SMR 167, CI 122-223) than in gold miners aged 60-74 (SMR 143, CI 109-184). As mentioned on p. 8, the incidence of stomach cancer normally increases with increasing age.

Time since first exposure

Shannon, 1987 found stomach cancer mortality peaked 10-19 years since first exposure to gold mining. After 30 years since first exposure no elevated rates of stomach cancer were observed. This pattern was confirmed by Kusiak et al., 1993, who found that statistically significant excess stomach cancer deaths appeared five to 19 years after the miners

began gold mining in Ontario.

Duration of exposure

In his 1987 study, Miller et al. found no relationship between duration of exposure and stomach cancer mortality.

Shannon et al. found that stomach cancer mortality was most increased in men exposed for between 10 and 14 years while durations over 25 years showed only a slight increase. When Shannon attempted to weight the exposure by year of first employment an inverse dose response was found, i.e. the SMRs decreased for those periods of longest weighted duration of exposure to dust. Shannon did not perform an age-specific analysis.

Kusiak et al., 1993, who reported that the average duration of employment in the gold mines was 10.8 years, found a statistically significant relationship between time-weighted duration of exposure to dust and/or chromium in gold mines and the SMRs for stomach cancer in gold miners under the age of 60. The association was strongest for weighted duration of exposure to chromium. For miners between 60 and 74, the association was not statistically significant.

Birthplace

Although it is well recognized that ethnic origin affects the incidence of stomach cancer in populations, the studies of Muller et al. (1986) and Shannon (1987) found that immigrant status was not a satisfactory explanation for the excess of stomach cancer among the gold miners since the SMRs were higher among those gold miners born in North America than those born elsewhere.

Kusiak et al.,(1993) found that with a latency of less than 20 years since starting gold mining in Ontario, there was no difference in the SMR for stomach cancer in miners born in North America (SMR 255, CI 139-428)or outside North America (SMR 270, CI 140-472). However, for a latency in excess of 20 years, only gold miners born outside North America showed a statistically significant increase in the SMR for stomach cancer (SMR 160, CI 115-218). (See Figure 8).

Histology

Using records from the Ontario Cancer Treatment and Research Foundation (OCTRF), Kusiak and colleagues compared histological types of stomach cancer in miners and controls. The table below is based on data in Kusiak et al's 1993 paper, analyzed by ODP staff (90). Stomach cancers in each age/exposure group are classified as either intestinal or diffuse according to OCTRF records. In all but the young gold miners, intestinal-type cancers make up about two-thirds of the stomach cancers. Among the young gold miners, 90% of the cancers are of the intestinal type. However, the numbers among the younger gold miners are small. For example, if two of their intestinal cancers were diffuse, then this group would exhibit essentially the same pattern as the other two groups.

Using logistic regression, a formal test of whether the younger gold miners had a higher proportion of intestinal-type cancers gave a p-value of 0.13, indicating that the observed difference is not beyond what would be seen by chance 13% of the time.

In the table below, the first number in each cell is the observed count of cancers and the second number is the corresponding percentage in the age/exposure category.

	Gold Miners			Other Miners			Hospital Controls
	Cancer Type			Cancer Type			Cancer Type
Age	Int.	Diff.	Total	Int.	Diff	Total	Int.	Diff	Total
< 60	9 90%	1 10%	10	2 66.6%	1 33.3%	3	13 59%	9 41%	22
> 60	15 62.5%	9 37.5%	24	9 69.2%	4 30.8%	13	43 63.2%	25 36.8%	68
Total	24 70.6%	10 29.4%	34	11 68.7%	5 31.3%	16	56 62.2%	34 37.8%	90

iii) Discussion

A dose-response trend is shown when an increase in the "dose" (exposure level including intensity and duration) corresponds to an increase in the "response" (usually a health outcome and in this paper a death from stomach cancer). A dose-response relationship is shown when more disease occurs after greater exposure to a substance. Epidemiologists usually demand verification of dose/response before they are willing to indicate that a causal relationship exists.

In the studies of the Ontario goldminers and stomach cancer, the only example of a dose/response comes from the Kusiak analysis which shows a statistically significant association with the time weighted exposure to chromium and/or dust in gold miners under the age of 60.

Coupled with the lack of a traditional dose response is the repeated finding that those who started working in gold mining after 1945 are at greater risk for stomach cancer than those who mined in earlier years. This finding has perturbed the investigators because it has always been assumed that dust levels and working conditions were more hazardous prior to 1945. On the basis of this assumption researchers expected that the rates of disease would also be higher among those workers who began employment before 1945.

There are several possible explanations for this phenomenon: No Causal Relationship
There is no occupational association and hence no causal relationship between work in a gold mine in Ontario and excess mortality from stomach cancer. Social Insurance Numbers.
The lack of a dose response in the Miller and Shannon studies may have occurred, in part, because of an under ascertainment problem among miners who started before 1945 and stopped working before 1965 when social insurance numbers (SINs)were introduced. This would mean that many deaths of miners employed during the dustier exposures for the longest periods of times may not have been captured. Most of the Ontario studies report higher SMRs for those gold miners who started working in the mines after 1945.

As noted by Kusiak et al., in their 1993 study of lung cancer in uranium miners , SINs were available for only 63.1% of the men in that cohort largely because the numbers were not issued until 1965. For the uranium miners with SINs the SMR was 225, whereas for those without, the SMR was 135. The social insurance number is a valuable aid in determining vital status. Twenty-five percent of those miners without SINs could not be identified as dead or alive versus all but five percent of those with SINs.

Muller et al., in their 1983 study among goldminers, had encountered the same problem. SINs were available for only fifty percent of his cohort approximately. Even using manual resolution methods available to them, Muller and colleagues were forced to reject almost fifty percent of the possible links.

An analysis conducted by ODP staff however, looked at the percentage of gold miners with SINs hired before and after 1945 (91). The post-1945 hires still included a fairly large proportion without SINs. The statistical analysis indicates that differential death ascertainment in the two groups (i.e., pre and post 1945) can only explain about 10% of the difference in the SMRs between these two groups. Factors other than lack of SINs must be considered to account for the 42% lower SMR for stomach cancer in those hired before 1945. Cohort age structure.
As illustrated in Figure 6, apparent SMRs for stomach cancer mortality are higher in gold miners first hired after 1945. However, Kusiak et al., 1993, has observed :

"The association between the excess of stomach cancer and starting gold mining after 1945 can be interpreted as an artefact of the strong associations between the relative excess of mortality from stomach cancers and both age and time since first gold mining. The mortality in the younger age groups of the miners who first worked in gold mines before 1945 would be only a small part of the mortality from stomach cancer seen in these miners."(p.124)

A regression analysis performed by ODP staff supports the concept that comparing SMRs for pre-and post-1945 hires is dangerous, as the age structures are drastically different for the two groups (92). Therefore, the SMRs of 322 and 123 in the 1987 paper of Muller et al.,are misleading

(64).

Because the pre-1945 gold miners are older, the expected number of deaths, as with most cancers, is higher. Since excess risk is limited to the younger age groups, the excess of observed deaths over expected is small.

In contrast, post 1944 hires tend to be younger and are therefore in age groups where the expected number of deaths from stomach cancer is low. Among younger miners, the relative risk of stomach cancer due to gold mining is high. The potential effect of this differing age structure on the SMRs is shown below with hypothetical numbers:

By ending the follow-up of the gold-miners cohort at various times, we can see that the pre/post distinction decreases as both groups reach older ages where baseline rates are higher and mining-associated relative risks are lower. This is illustrated in the table below:

The Effect of Age - Regression Analysis
To further examine the effect that age and other factors have on the SMR for stomach cancer, Poisson regression was performed on the data grouped by era of hire, age, age at hire, number of years of mining gold, and active versus inactive status (according to whether a miner was listed as employed or not in the MMF). The work was done in collaboration with Professor Paul Corey of the University of Toronto and full details of this analysis are reported in Appendix B of this report and an ODP memo (93).

The main findings of this regression analysis are summarized below and are based on what was determined to be the simplest model that gave a good fit to the data.

(1) When age, age at hire, years of gold mining and active status are controlled for, there is not a significant difference in risk between the pre- and post-1945 hires (p=0.30)

2) Active miners have a much lower risk of stomach cancer (p<0.0001), a fact that probably reflects how unlikely it is that a miner with stomach cancer continues to work, but also reflecting the generally better health of those who are able to continue full time work.

(3) Risk for stomach cancer increases with age at hire into gold mining (p=0.0009). It is unclear whether this represents an actual effect of later onset of exposure or represents some other unidentified characteristic of those who start gold mining at a later age.

(4) Years of gold mining and attained age are not independent risk factors (p=0.006). For younger miners, relative risk for stomach cancer increases with number of years of gold mining, whereas for the oldest miners, there appears to be no relationship between years of mining and relative risk - see Figure 9. There is no single age where risk drops off: the model assumes a continuous decline in risk with age for any particular exposure level. For example, the relative risk for 25 versus 2.5 years of gold mining drops from over 6 at 45 years of age to less than 1 at 70 years of age. For different gold exposures, these numbers would be different. Overall, though, according to this model, the upward trend in risk with years of gold mining is statistically significant below age 62 .

Choice of the Reference Population
As mentioned previously, Shannon, 1987, analyzed stomach cancer mortality among gold miners with the Northern Ontario male population as the control group and observed a lower SMR in both the North American-born and non-North American-born gold miners from that observed when the Ontario male population was used as controls.

To see if stomach cancer in the gold miners had a different pattern with age or calendar time from that in the Northern counties, three comparisons were made:

• Northern Ontario males versus all of Ontario males
• gold miners versus Northern Ontario males
• gold miners versus all Ontario males

The results, shown graphically in Figures 10-12, indicate that:

• The Northern Counties have higher stomach cancer rates than Ontario as a whole, but this elevation does not vary with age or across calendar time: rates are simply 20% higher across the board. The unusual high SMR on Figure 10 in the youngest age group is based on a small number of deaths in the Northern population.
• When gold miners are compared to either the Northern Ontario male population, or the Ontario male population, there is a statistically significant trend for decreasing relative risk for stomach cancer with age. There is no evidence for an effect of calendar time.

In other words, stomach cancer in the gold miners does not follow the same trends as that in the males of Northern Ontario when both are compared to the Ontario male population. The gold miners' relative risk of stomach cancer decreases with increasing age, while the relative risk among the Northern males compared to Ontario males remains constant with age.

Thus Shannon's 1987 comparison using the Northern population as a reference group would have the effect of reducing the SMR, but the present age-stratified analyses provide strong evidence that the excess of stomach cancer among gold miners is due to something other than merely being Northern residents.

Other Considerations
The make-up of the cohort also reflects the following:

The gold miners had to have been alive and working in 1955 or later to be in the cohort. Those who fell ill, died, retired, or switched employment to a position not requiring an annual x-ray before 1955 could all have been lost to the cohort, even though they might ultimately have died of stomach cancer.

With a relatively uncommon cancer such as stomach, under ascertainment of deaths could have an even more profound effect on the SMR than was apparent in Kusiak's later study of lung cancer among uranium miners.

In Kusiak et al., 1993, the miners were followed until the end of 1986. Included in the analysis was any miner who had 60 months of experience and had a chest x-ray between 1955 and 1977. While miners continued to be added to the cohort it is unlikely that there would be sufficient follow-up to examine the real rates of mortality for those miners who commenced employment after 1967.

Detailed histological typing for the stomach cancers among the gold miners was obtained for the first time in the 1993 study of Kusiak et al. Given the apparent absence of a true dose response and the indication of high rates of intestinal cancers among younger workers, (see analysis on p. 32), it may be that it is only intestinal cancer which is associated with work. Although admittedly speculative, a dose response based on both histological types could be difficult to demonstrate looking at the entire cohort.

iv) Conclusions

• All analyses of the Ontario cohort and two of three international studies report elevated rates of stomach cancer among goldminers.
• The highest SMRs for stomach cancer are observed in goldminers who began work in gold after 1945. However, as Kusiak et al. postulated and Tomlinson has confirmed, the differences in the cohort age structure pre and post 1945 are responsible for this artefact.
• Under ascertainment problems due to absence of SINs in pre-1945 hires can account for only about 10% of the observed differences between pre and post 1945 SMRs.
• The increase in stomach cancer appears 5-19 years after first gold mining and peaks between 10 and 19 years, followed by an apparent decline.
• The Ontario studies consistently show that goldminers exhibit statistically significant elevated mortality rates for stomach cancer. The overall SMRs vary from 136 to 157, with the highest SMR reaching 463 among those with the highest time-weighted index of exposure to chromium and age less than 60.
• A dose response relationship has been established by Kusiak et al., 1993, for the time weighted duration of employment in gold mines for men under the age of 60, and in particular for the time-weighted exposure to chromium and/or dust. This relationship was not detected by Shannon,1987 or Miller, 1987, both of whom used duration of employment as a surrogate for exposure.
• There is strong evidence that goldminers under the age of 60 are at greater relative risk for stomach cancer than those over 60.
• The evidence consistently demonstrates that it is unlikely that place of birth is an important factor in the increased stomach cancer mortality among Ontario goldminers.
• An increase in the intestinal type of stomach cancer among younger miners may be a reason for the elevated rates of stomach cancer mortality within the 5 - 19 year window since first mining gold.

3. What is known about potential occupational causes of stomach cancer?

i) Dr. Stock's Review

In a 1994 Panel commissioned review of the literature on stomach cancer, Stock addressed the above question by summarizing that:

"In reviewing this literature one is struck by the huge number of studies demonstrating a statistically significant association between occupation and stomach cancer despite enormous variation in methods and approach and the inherent difficulty in demonstrating such associations in occupational cancer epidemiology....

While no one study is methodologically strong enough to provide unequivocal evidence of a causal relationship between stomach cancer and the occupation under study and none has quantitative exposure measurements, there are now numerous examples of excess risk of stomach cancer in various occupational groups supporting the hypothesis that occupational exposures can contribute to the development of stomach cancer....

Although there are probably at least 100 studies which have examined a link between occupation and stomach cancer, few articles in the literature have attempted to explain potential mechanisms for occupational gastric carcinogenesis. The main theories found in the literature have arisen in an effort to explain stomach cancer in coal miners and were described by Ames who suggested the following hypotheses: (emphasis added)

1. Poly-aromatic hydrocarbons (PAHs) especially benzopyrene may be absorbed by coal mine dust. Absorbed precarcinogens may be activated by the (cytochrome)p-450 oxidase enzyme system and lead to intragastric production of carcinogens that attach (to) mucosal tissue and induce gastric carcinoma. PAHs such as benzopyrene are known to transform epithelial cells and initiate cancer. Combustion products of coal have been shown experimentally to be carcinogenic to the gastric epithelium in mice and in tissue culture (Weinberger et al). A similar PAH hypothesis is proposed by Nutt as a likely explanation of the stomach cancer found in rubber workers. PAHs are also found in lubricating oils and are a possible explanation of increased stomach cancers found in bearing plant workers found by Park et al and Silverstein et al. Interestingly the sharp decline in gastric cancer in many developed countries parallels the drop in the use of coal burning in homes and this cancer is high in those countries where coal burning for cooking is still common.

2. Exposure to dust in general may cause gastric cancer. Respirable dust may be subject to macrophage scavenging, brought up through mucociliary clearance and swallowed as with other inhaled particles. Coal mining dust exposures include iron dust, iron oxides from welding, other metals found in coal, rock dust, particulate from blasting, asbestos insulation, coal shuttle brake linings dust and diesel particulate. Coal miners may also have been exposed to other non-occupational environmental sources of dusts such as soot from coal combustion from cooking and/or heating or lived near nuisance dusts or soil erosion dust. This hypothesis is supported by studies of quarrymen and some air pollution studies. Pham et al propose an interesting mechanism for the carcinogenesis of general dust exposure in their efforts to explain the high rate of stomach cancer in iron ore miners. They suggest that the inhaled iron oxide dust may have acted by production of free radicals arising from surface activity by a mechanism of oxygen reduction which is greatly increased in freshly generated dust. This physicochemical surface activity has also been found in silica and asbestos fibre dust (Costa et al 1989). It may also be relevant in the high rates of stomach cancer found in those in grinding occupations in bearing plants.

3. Gastric cancer risk may be associated with exposure to nitrosamines, their precursors, or to nitrosation facilitators. Coal miners were exposed to nitrosamines and nitrogen oxides released from coal by pyrolysis; nitrates from inhalation of particulate after blasting (nitroglycerin or ammonium nitrate); dietary sources in smoked or salted fish or bacon (smoked foods also contain benzopyrene); drinking water sources from wells contaminated with high levels of nitrates (1981 studies by Armijo et al suggest a co-factor of arsenic and selenium to explain nitrate exposure and gastric cancer); nitrosation enhancement from chewing tobacco and/or bacterial contamination from sewage polluted water, poor dental health, and poor preservation of and storage of food. Similarly nitrosamines may be implicated in stomach cancer in rubber workers (Nutt et al) - exposure was very high when N-nitrosodiphenylamine was in use. Nitrosamines are also found in soluble oil and synthetic cutting fluids and may be relevant to the high stomach cancer rates found in bearing plant workers.

Stock continues....

Another hypothesis was proposed by Meyer et al. to explain stomach cancer in coal miners but was later refuted by Ames and Gamble and not supported by subsequent studies. Meyer et al. suggested that stomach cancer risk is increased when particle retention in the lungs is decreased, i.e., particles are more rapidly cleared to the mouth and swallowed when there is no pulmonary impairment; gastric cancer risk would be lower when lung clearance is reduced because of pulmonary function impairment.

These hypotheses are of interest and could potentially explain a high proportion of the observations of increased mortality from stomach cancer in various occupational groups. Alternative mechanisms are obviously possible and would be relevant to explain the Kusiak et al suggestion that exposure to chromium is the main cause of the high rate of stomach cancer among Ontario goldminers observed in that study." ⁽⁵⁾

In addition to nitrosamines, there is strong experimental evidence to show an association between other nitroso compounds (e.g. nitrosoureas) and stomach cancers (99). In fact, some of these compounds are the chemicals of choice to induce cancer of the glandular stomach in experimental animals. These compounds appear to act as precursors that are easily converted to the ultimate carcinogens.

As in nitrosamines, nitrosoureas may be produced from nitrite and nitrate by way of chemical reactions that are believed to be possible in a low acid stomach environment. Interestingly, this environment is commonly observed in the stomachs of individuals with stomach cancer. It has thus been suggested that any factor that increases exposure to nitrates and other nitrogen compounds would also increase the risk of stomach cancer (3).

ii) Conclusions:

• Numerous studies show statistically significant associations between a variety of occupations and stomach cancer.
• No specific occupational substance has been conclusively identified as the causal agent.
• Dusty work environments are known to be associated with elevated risk of stomach cancer. The action of dust particulates may be one of mechanical irritation or disruption to the mucosal lining, permitting acid/mechanical damage or cellular contact with carcinogens.
• There is strong experimental evidence to show an association between certain nitroso compounds and stomach cancer.

4. Are any of these and other potential causes relevant in the Ontario gold mining environment?

Gold is found throughout the earth's crust but usually very sparsely, ranging from 0.002 to 0.005 grams per ton. This metal frequently occurs in a free state or as an alloy with other metals such as silver, copper, aluminum, platinum, zinc, palladium and tellurium. Gold commonly occurs in veins among rocks and ores of various other metals such as copper, iron, lead, zinc, antimony and arsenic.

With a low degree of chemical reactivity, gold is generally stable under most environmental conditions. It is not known to be toxic to humans or animals when ingested or inhaled. Occupational health hazards associated with gold are attributed to its extraction by underground mining (as described below), largely as a result of worker exposure to airborne contaminants generated by the mining and milling processes.

Epidemiological studies have reported a strong relationship between stomach cancer and gold mining. Figure 13 illustrates the typical processes carried out in a gold mine. The 1994 review by Stock found that these studies were not designed in such a way as to be able to implicate any specific occupational substance (87) and the evidence of a specific causal agent continues to be speculative. Nevertheless, a number of agents she suggested as possible causes of stomach cancer can be found in the Ontario gold mining environment.

i) Airborne Dusts

Studies of various occupations have suggested an association between dust exposure and increased stomach cancer mortality (85,69). In particular, elevated risks have been reported for coal miners (2,7,19,51)) foundry workers (21) and cement workers (54). The combination of dust and PAHs was implicated in some cases (70), while in others it was thought to be the production of free radicals from cellular activities to reduce oxygen in freshly generated dust (79). The latter has been suggested as a factor in the etiology of carcinogenesis for silica and asbestos (17), as well as for certain metal dusts (87). Metal dusts were implicated in the development of stomach adenocarcinoma in male workers of dusty occupations in Los Angeles, California (106). Some of the metal dusts include beryllium, chromium and nickel.

Wright also found an elevated risk of stomach adenocarcinoma in workers in dusty jobs (proportional incidence ratio = 1.3, 95% CI = 1.2-1.4) after controlling for ethnicity, immigration and socioeconomic status but not cigarette smoking (105). It was suggested that abrasive particulates in the stomach may disrupt the mucosal barrier, permitting either acid or mechanical damage, or cellular contact with carcinogens that would not ordinarily occur in the presence of an intact barrier. A similar hypothesis for mechanical irritation from particulates in food stuff has been offered as a cause of stomach cancer (78).

Dust in underground gold mining is produced by such operations as drilling, blasting, scaling, loading, crushing and moving of broken rocks (mucking). While water is used for dust suppression in many of these operations, this practice has not always been applied in the past. Airborne dust condition in underground mines was made worse in the past by the lack of adequate ventilation.

According to personal accounts from retired goldminers, excessive dust exposure occurred in such ore handling operations as crushing or dumping of ores from one level down to another through ore passes. Dust records for Ontario gold mines were not available until 1958, when konimeter measurements of airborne insoluble particulates were made as an indication of underground dust levels. Average levels from early konimeter measurements were as high as 460 ppcc, well above the recommended guideline of 300 ppcc (26). Since then, levels have gradually decreased (by almost two fold to 250 ppcc between 1960 and 1975) due to improved underground ventilation in 1960's.

High inhalation exposure to airborne dust was made worse by heavy breathing as a result of intensive physical work and by not using respiratory protection of any kind. The practice of using respiratory protective equipment has never been made mandatory in underground gold mining and is not common even today. For individuals working in a dusty environment, some of the inhaled dust particles would be cleared from the lungs and swallowed, increasing the risk for stomach cancer (56,83). Hand-to-mouth contact was another likely route through which dust from gold mining can enter the stomach.

Apart from dust in general, there are also specific contaminants of gold mining dust which may be associated with an elevated rate of stomach cancer. These are separately discussed below:

a) Arsenic

IARC considers arsenic a Group 1 carcinogen with sufficient evidence of carcinogenicity in humans (32). It does not exclude any specific forms or compounds of arsenic in its evaluation and includes miners among those occupations potentially exposed to arsenic.

Recognized mainly as a lung and skin carcinogen in humans, arsenic has also been shown to be associated with cancers of other sites. Although inconclusive, there is evidence to suggest that exposure to inorganic arsenic compounds may be related to the development of stomach cancer. In a study of Cornish tin miners, elevated rate of stomach cancer (SMR = 890) was reported for surface workers involved in the roasting operation of the trivalent arsenic trioxide (30). A higher rate was also noted in underground miners but the increase was not significant and did not appear to be associated with dust exposure underground. Arsenic trioxide was also suggested as a possible cause associated with an increased risk of stomach cancer in a group of Swedish glassblowers (relative risk = 6.4, CI = 3.0-14.0) (102).

Arsenic is found naturally with gold deposits, generally in the form of pentavalent arsenopyrite and often in high concentrations. Although it is found in most Ontario hard rock mines, inorganic arsenic in gold mines is commonly found in greater concentrations. Therefore, the likelihood of arsenic exposure to Ontario gold miners is not in doubt, the question is on the bioavailability of the inhaled inorganic arsenic. Pentavalent arsenopyrite is relatively inert when undisturbed but may become more soluble, and more bioavailable, when disturbed by mining process, natural leaching, microbial action, blasting and contact with water. Urinary levels in Ontario goldminers do suggest that at least a portion of the inhaled inorganic arsenic is bioavailable (40).

It is also reported that arsenic trioxide, as a by-product of gold processing, has also been stored in large quantities underground (10). To what extent this contributes to the exposure of Ontario goldminers to arsenic is not known. However, there is anecdotal evidence indicative of significant exposure in goldminers, as numerous symptoms commonly related to arsenic exposure such as dryness, itching, burning and cracking of the skin have been observed (10). Arsenic related abnormalities such as pitting of the nails, thickening of the soles and palms, linear markings, hyperpigmentation of the hands, feet and legs, and hyperkeratosis were also noted.

On the basis of this study and in conjunction with other findings, stakeholders and the Ontario Ministry of Labour agreed during the consultative process for the designation of arsenic that this substance in underground hardrock mining is bioavailable to a certain extent (101).

b) Asbestos

IARC has designated asbestos as a Group 1 human carcinogen not only in lungs but also in various sites including the gastrointestinal tract (32).

Muller in 1986 postulated the association between the presence of mineral fibres, including asbestos, and lung cancer. Although this work did not look at other cancer sites, a link between asbestos and gastrointestinal cancer has been identified (104). In its report of 1990, the Industrial Disease Standards Panel confirmed the finding by the Royal Commission on Asbestos that occupational exposure to this substance is causally associated with cancer of the gastrointestinal tract, including the stomach (37).

Asbestos may be present in the mining environment both intrinsically and extrinsically. Veins of tremolite, a form of asbestos in the group amphiboles, have been identified in underground mines (88). In one U.S. gold mine, mean total fibre concentration in underground air as measured by transmission electron microscopy was 4.8 fibre/cm³ (range 0.7-11.8 fibre/cm³) (25). Over 80% of the fibres identified were of the amphibole type.

The presence of asbestos in the natural state may not present much of a hazard to non-asbestos miners. However, once disturbed and made airborne, its presence in dust can be a hazard to underground miners. Asbestos can also be brought into the mining environment in its processed form. It is used in the brakes of motorized mining equipment and in insulating materials around pipes.

c) Silica

According to IARC, crystalline silica is a probable human carcinogen (Group 2a) with limited evidence of association to lung cancer in miners and other workers (32). With respect to stomach cancer, it has been linked to industries related to silicosis in one study (41) although other studies were unable to confirm the association (8, 84).

Silica is present in the Ontario gold mining environment, with a concentration of 15-35% free crystalline silica in gold ores. Since similar concentrations were found in total dust samples collected from Ontario gold mines, total dust was measured historically as an indicator of potential silica exposure in these mines.

Since 1960, dust levels in Ontario gold mines have gradually decreased so that the 1975 level was about half of that measured in 1960 (26). In the 1970's, air sampling measurements made on respirable crystalline silica showed average levels consistently at or below the current TWAEV of 0.1 mg/m³.

d) Chromium

IARC recognizes chromium in its hexavalent state as a Group 1 carcinogen with sufficient evidence of carcinogenicity in humans, while the evidence for metallic and trivalent chromium compounds is insufficient (34).

Like arsenic, chromium is widely distributed in Ontario ore bodies associated with gold. It commonly occurs as fuchsite (a chromian mica) or chromite (a chrome oxide), neither of which involves chromium in its hexavalent form. There is no evidence to suggest that the hexavalent state can be converted from the other forms within the human body (5). It remains to be determined if such conversion can take place in the gold mining environment. As with other agents discussed in this section, the possibility that chromium, perhaps in combination with other factors, can contribute to the increased risk of stomach cancer in Ontario gold miners cannot be dismissed.

In fact, chromium has been suspected as a cause of the excess of stomach cancer amongst Ontario gold miners (44). This conclusion was made on the basis that stomach cancer mortality was more closely associated with chromium exposure than with any other factors examined. Interestingly, a review of the mines which showed high chromium content revealed that most of them began operation only after 1938 and not before. If prolonged and excessive exposure to chromium were indeed a contributing factor in the development of stomach cancer, this would help to explain the finding that the highest excess mortality from stomach cancer is observed in younger miners who worked in Ontario gold mines after 1945.

ii) Polycyclic Aromatic Hydrocarbons (PAHs)

Certain PAHs such as benzo[a]pyrene are known to be potent human carcinogens associated with various types of cancer in the body (32). Some may act as precarcinogens which become activated in the body and lead to the formation of carcinogens that attack the stomach mucosal tissue and induce gastric carcinoma (87).

In the mining environment, PAHs are found in diesel emission, blasting smoke and in oil mist generated from the use of straight lubricating oils. These contaminants may be adsorbed onto airborne particulates which can then be inhaled. Some of these inhaled particulates are cleared from the lungs and are swallowed, allowing the PAHs to enter the digestive tract. In addition, PAHs can also be delivered to the digestive tract through hand-to-mouth contact as discussed later in section 5, iii.

a) Oil Mist

IARC has designated oil mists into two groups: untreated and mildly treated oils (Group 1), and highly refined oils (Group 3) (31). In underground mining, oil mist refers to airborne particulates generated from oil used to lubricate drills and other equipment. The predominant lubricant for drills and motorized equipment used in underground mining is of the first type.

The introduction of diesel equipment into the mining environment in the 1960s complicates the measuring of oil mists. They are hard to distinguish from oil in diesel emissions. Any dust sample could contain both diesel soot and oil mist (23). Nevertheless, a study of Finnish sulphide ore miners reported that the average airborne concentration of oil mist during drilling was as high as 3 mg/m³ in the 1970s, ranging from 0.1 to 17 mg/m³. The authors estimated that underground mining exposure to oil mist between 1950 and 1960 could have been double that of the 1970s (1).

The Ontario Ministry of Labour's bipartite Occupational Exposure Limits Task Force conducted a review recently of the current exposure limits for 101 substances and recommended lowering the current time-weighted average exposure value (TWAEV) for mineral oil mist from 5 mg/m³ to 1 mg/m³, and the current short term exposure value (STEV) from 10 mg/m³ to 3 mg/m³. Some of the other Task Force recommendations have been implemented, but those pertaining to mineral oil mist have not. The members eventually agreed to maintain the current guidelines due to the potential economic impact of reducing them (73,77).

The United Auto Workers (UAW) have petitioned the Occupational Safety and Health Administration (OSHA) in the US to consider a reduction of the time-weighted average limit for worker exposure to oil mist to 0.5 mg/m³ from the current 5mg/m³ (6). Unlike the auto manufacturing sector in North America, in which exposure levels as low as 0.2 mg/m³ are now achieved, the underground mines and particularly the more confined environment of many Ontario gold mines continue to be associated with much higher oil mist levels.

b) Diesel Emission

IARC has found that "Diesel engine exhaust is probably carcinogenic to humans"(Group 2A) (33). This emission is a complex mixture of particulates, gases and vapours that include PAHs and other potential carcinogens.

Diesel equipment was first introduced to Ontario underground mining in the early 1960's, and its use underground has been a continuous health concern among mine workers and management. As a result, diesel equipment was gradually replaced in some mines by electrical powered machinery during the late 1970's and 1980's. Today, many Ontario gold mines still use diesel equipment underground and are absorbing the higher cost of improved ventilation. It has been postulated that improved ventilation may not help reduce exposure as was once assumed, since PAHs remain in the mine air longer than particulate and are not removed completely with the ventilation (100).There are presently no Ontario standards for occupational exposure to diesel emission. This issue is currently before the Ontario Mining Legislative Review Committee which is recommending an exposure level of 1.5 mg/m³.

iii) Nitroso Compounds

Nitrate and nitrite are commonly found in the environment, foods (additives and preservatives) and in various occupational environments. As mentioned earlier, salts of nitrate and nitrite may be converted to nitrosamines and nitrosoureas by chemical reactions with amines in a low acid stomach environment. Many of these nitroso compounds have been shown to be carcinogens and a few can induce stomach cancers in experimental animals.

In underground mining, nitrate salts can be found in the airborne mixture of gases, vapours and particulates generated after blasting with explosives. These explosives were either nitrogen-glycerin based (before the 1950's) or a mixture of ammonium nitrate (94%) and fuel oil (6%) called ANFO used after the 1950's. In some mines, water gel explosives are also used.

The largest consumption of explosives is for development and production blasting. These operations were initially carried out in two stages during normal workshifts. In the first stage, the centre of the rock face is blasted and miners would often be excessively exposed to smoke, dust and gases from the first blast as they walked through this mixture to prepare the remainder of the rock face for secondary blasting. In gold mines, such a mixture could not be easily cleared owing to the confined work space and poor ventilation in the past.

Few miners are now exposed to such blasting since the introduction of central blasting, a practice by which the initial blast takes place between shifts or when workers are either on the surface or confirmed to be in safe, unaffected areas. With adequate ventilation, it takes about 3 to 4 hours for the concentration of gases to return to pre-blast levels. However, secondary blasting still occurs today and has not changed much over the years. This type of blasting (for making raises, muck spillage or clearing obstructions) could take place any time during a shift and often at close proximity to miners working underground.

iv) Conclusions:

• Goldmining is a dusty occupation;
• Goldminers are likely occupationally exposed to many known and suspected human carcinogens. These include arsenic, asbestos, silica, chromium, PAHs, oil mist, diesel emission). Of these, asbestos and hexavalent chromium are known to be potential gastrointestinal carcinogens.
• Goldminers could also be exposed to nitroso compounds or precursors of such compounds. There is experimental evidence that some of these nitroso compounds are associated with stomach cancers.
• Ingestion is a likely route of entry for any carcinogens to which Ontario goldminers may be exposed.

5. What, if any, are the differences between gold mining and other kinds of hardrock mining in Ontario?

Further to the agents discussed above, the Panel also investigated other aspects of Ontario gold mining which may be related to stomach cancer. These focused on differences between gold mining and other types of hardrock mining in Ontario. In her report to the Panel, Stock indicated that:

"In general, the gold mines began operating considerably earlier than other mines (1910-1949) and closed down much earlier (1950-1970). Thus goldminers may have tended to be older than the other miners. The mines were known to have had extremely high dust levels prior to 1950 with a silicosis SMR of approximately 850, high rates of silicotuberculosis and measured dust levels in the 1930's and 40's often above 1000 particles/ml. Although dust levels in gold mines and non-gold mines may have been comparable at any given period, dust exposure levels were likely much higher among miners who worked prior to 1950 and thus the cumulative exposure levels were likely highest among goldminers..."

The Panel's investigation also revealed there was in general a notable difference in mining methods between gold and other hardrock mining. Namely, gold which usually occurs in small veins necessitates underground miners to often work in narrow workplaces and confined spaces. The methods used for mining gold are of the low-tonnage type and are less mechanized than bulk mining methods used to extract massive (e.g. nickel, copper and iron) or tabular ore bodies (uranium) (88). Such low-tonnage methods require work that is more physically demanding and close to the rock face, thereby resulting in a greater potential for worker exposure to airborne contaminants (e.g. oil mist, diesel emission and dust) than would be with other methods.

Ontario goldminers would also be more exposed to airborne crystalline silica and inorganic arsenic than other miners. The amount of crystalline silica in the respirable fraction of airborne dust in mining operations is directly related to its content in the ore and host rock being broken (26). Higher concentration of crystalline silica as quartz occurs in gold ore (15 to 35 per cent) than in nickel or iron ore (up to 10%) or uranium ores in the Bancroft area (5 to 15%). The uranium ores in the Elliot Lake area contain 60-70% crystalline silica. Since the average length of work for uranium miners is 1.5 years, compared to 10.8 in Ontario goldminers, cumulative silica exposure in these Elliot Lake workers would in general still be far less than the exposure experienced by Ontario goldminers.

Arsenic concentration in Ontario gold mines varies widely from undetectable levels to levels as high as 1.6% of the host rock (43). Arsenopyrite is also found combined with nickel ore but generally in lower concentration than in gold ore. Arsenic levels in Sudbury ore range from 0.096% to as low as 0.0004% (96).

Other notable differences between gold mining and other hardrock mining in Ontario include:

I) Backfill

Backfill refers to the process by which waste material is used to fill the void created by mining an ore body. This material can consist of gravel, waste rocks, cement, mill tailings or a combination of these mixed with sand. It is used mostly in 'cut-and fill' operations and was first introduced in Ontario gold mines in the 1940's.

Although backfill is not unique to gold mining and is also used in base metal mines (e.g. nickel) in Ontario, only the gold mines are known to have used liquid mill waste to backfill (82). Even after washing and other treatments, such mill waste could still contain significant amounts of harmful contaminants. For example, 2.41 mg/l and 12.8 mg/l of arsenic were found in recent effluent water samples from the backfill and tailing, respectively, of an Ontario gold mine (18). The Ontario effluent limit for total arsenic is 0.5 mg/l (76).

At first, backfill from the surface was brought to the desired location underground by dumping it down vertical chutes between levels. This process was extremely dusty since the backfill was dry going down the chutes. After the 1960's, hydraulic backfill was introduced which allowed this material to be transported in pipelines. This material contains 40 - 60% water and is transported in the form of a slurry; thus very little dust is generated.

ii) Aluminum Powder

Many Ontario goldminers were exposed to large quantities of aluminum powder as a prophylactic agent against the development of silicosis. This powder (a finely ground mixture of mostly aluminum oxide, metallic aluminum and iron oxide) was dispensed as an aerosol which miners were compelled by working procedures to inhale each day before their shift. In the lungs, this powder was believed to be capable of binding to and coating crystalline silica to prevent responses of the lungs that would otherwise elicit the cellular changes which can lead to silicosis.

In Ontario, the practice of dispensing aluminum powder to miners began in 1943 and was rapidly adopted by the mines. The greatest application in Ontario was in gold mines (37 gold mines by the end of 1944), although six uranium and one silver mine also adopted the practice by 1958 (80). There was no record of usage in nickel, copper or other Ontario mines. The recommended regimen based on effective dose was deep mouth breathing for 10 to 20 minutes at an airborne concentration of 35.6 mg/m³, which resulted in significant respiratory (estimated alveolar burden of 375 mg/year) as well as gastric exposure. Although there was limited evidence of harmfulness, a scientific task force concluded that further studies were required on the biological effects of this powder in humans. Since the effectiveness of aluminum powder against silicosis was itself doubtful and inadequate by scientific standard at the time, the practice was halted in 1979.

Aluminum does not appear to have an essential physiological role in humans and its toxicology is not well understood. This element is poorly absorbed in the body and is efficiently excreted. In the human stomach, aluminum oxide acts as a buffer against the acidity and forms ions which can react with other substances to form aluminum complexes. It is not known what other effects these complexes may have on the stomach and the remaining gastrointestinal tract.

Kusiak dismissed aluminum powder as a causal agent of stomach cancer in Ontario gold miners, on the basis that no apparent increase in this cancer was seen in uranium miners who were also exposed to the powder(44). However, the average duration of employment for uranium miners is 1.5 years while that for goldminers is 10.8years. Furthermore, in Ontario the use of aluminum powder in gold mines commenced 15 years earlier and halted later than in uranium mines. Therefore, this conclusion may be inappropriate since the exposure to aluminum oxide in uranium miners could have been insufficient to permit this substance to elicit an effect similar to that observed in Ontario goldminers.

iii) Underground Working Environment

While gradual efforts have been made to lessen mining hazards, other unhealthy working conditions long tolerated by underground goldminers have changed very little. For example, underground washroom facilities and potable water were only recently made available to Ontario gold mines and, in general, later than in other metal mines. For example, Ontario uranium mines, most of which opened in the 1950's, made provision for potable water and washing facilities underground as part of their initial operational plans. These facilities soon became available in Ontario nickel mines but long before they were introduced into the gold mines.

In a mine that has been extensively excavated, underground refuge stations and washroom facilities are often far away (up to a mile) from the work areas and, because of the lengthy travelling time needed, are not always used. Instead, it is customary for underground miners to rest and have meals where they work, where the level of dust and other airborne contaminants may be considerable. A recent tour of Ontario gold mines also showed that these miners are routinely covered in dirt and grease from work and their hands are often dirty while they have their meals. The likely ingestion of particulates from food stuff in these conditions (poor personal hygiene, dusty environment and few washing facilities) may affect the development of stomach cancer.

The lack of washing facilities may be significant since it has been postulated that the normal mucosal barrier may be overcome by abrasives or irritants (16). Peters noted that the highest risk of stomach cancer is observed to occur in the antrum-pylorus area of the stomach where the tissue lining is regularly under muscle pressure (78). The forcing of fluid containing particulates through this area could create a direct mechanical effect. He speculated that increasing dietary cleanliness may have contributed to the downward trend in stomach cancer in industrialized countries. In goldminers, irritation of the stomach lining could be attributed to ingestion of particulates such as aluminum powder, dust in general and contaminants in foods.

Before the 1970's, potable water was not available underground except in containers which underground miners carried with them to their work areas. Even now, it is only available in refuge stations which are few and often far from areas where miners are working.

Miners were also known to drink water intended for mining processes such as drilling or dust suppression - water that was not considered potable.

Samples of process water from a few Ontario gold mines were recently collected by the Ontario Ministry of Labour (MOL) and analyzed by the Ontario Ministry of Environment (MOE). Most of the parameters examined (e.g. PAHs, mercury, cyanide and metals) were well within standards for Ontario drinking water, while others such as nitrite/nitrate and arsenic exceeded their respective standards in a few of the samples. It should be noted that these results do not reflect an on-going monitoring process nor water quality in the past.

iv) Conclusions:

• Low-tonnage mining methods are used in Ontario gold mines. These methods require more manual work to be performed in more confined spaces than bulk mining methods generally used for other hardrock mining. Goldminers are therefore more exposed to airborne contaminants.
• In Ontario, aluminum prophylaxis was used primarily in the gold mining industry and, collectively, goldminers had the longest exposure to the aluminum powder.
• Backfill with liquid mill waste was used primarily in the gold mining industry. Depending on the type of mill waste and its composition, airborne contaminants generated from this backfill may be more hazardous than those from backfills of other types of mining.
• Gold mines are some of the oldest mines in Ontario and underground facilities for washing and clean water were made available later than in other mines. Even today, these facilities in Ontario gold mines are generally inferior. It is questionable how often underground goldminers in the past have actually used these facilities in their daily work.

6. Are there other risk factors that could affect the pattern of stomach cancer?

i) Diet

Diet appears to play an important role in the development of stomach cancer. For example, studies have shown that increased risks of stomach cancer may be associated with a high intake of smoked, salted, fried or starchy foods (28,72,49,58,55), as well as exposure to high levels of nitrite and nitrate in foods and drinking water (3). It is hypothesized that excess salt in the diet may irritate the stomach lining, while nitrite and nitrate in the stomach can form N-nitroso compounds, many of which are carcinogenic in animals and a few are human stomach carcinogens (see nitroso compounds under 2B.3).

On the other hand, fruits, vegetables and specific substances such as vitamins A, C and E found in these foods appear to have a protective effect against stomach cancer (52,58,55) and other cancers in the gastrointestinal tract (46). It is suggested that some of these substances may act by interfering with the formation or reaction of chemical carcinogens or pre-carcinogens such as N-nitroso compounds.

While a deficiency in dietary vegetables and fruits could certainly be a contributing factor in the increased stomach cancer rates of the general Northern Ontario population, this does not explain why elevated stomach cancer mortality is specifically confined to goldminers. It would be difficult to argue that the diet of goldminers in rural Northern communities differed substantially from that of other Northern mining groups, none of whom showed any excess mortality from stomach cancer.

ii) Cigarette smoking and alcohol consumption

In coal miners, light smokers (one to ten cigarettes a day) were found to have significantly higher stomach cancer rates than non-smokers (56). This led some to postulate that light smoking may stimulate the lungs' clearance process (in contrast to heavy smoking which would impair the process) thereby introducing more carcinogens into the stomach (56,24).

A recent population based case control study analyzed lifetime tobacco use and occupational histories (9). Subjects who had ever smoked cigarettes had a statistically significant increase in stomach cancer (OR=1.5, CI=1.2 to 1.8) and the risk increased with increasing pack years. The risk was highest among black men and white women and not significantly increased in white men (OR=1.2, CI=.9-1.6). Increased risk among the white men was associated with the occupations of farmer, mechanics, assemblers, or machine repairmen. The authors speculate about the potential role of diesel exhaust and/or asbestos.

However, Kusiak et al., 1991 (43) found no material difference in smoking habits between gold and nickel/copper miners. Therefore, cigarette smoking alone cannot explain the elevated risk of stomach cancer in Ontario goldminers. In fact, the evidence regarding cardiovascular disease among miners in general, does not show the typical pattern of increased risk characteristic of heavily smoking populations.

Results of studies of alcohol and cancers of the stomach have been inconsistent, but generally not supportive of a causal association (46). Ontario miners' mortality from cirrhosis of the liver shows a statistically significant deficit (SMR=77, CI=66-88) from this cause and suggests that alcohol consumption in Ontario miners is less than that of other men in Ontario (45). A deficit of morbidity from cirrhosis of the liver was also confirmed by Muir and Julian in a study of cancer morbidity among nickel/copper workers (60).

iii) Ethnicity and place of birth

World-wide, the rate of stomach cancer varies as much as ten-fold, with some of the highest rates occurring in eastern Europe and Japan (98). The rate is found to decrease slowly in populations moving from a high-risk to a low-risk country; thus suggesting a strong environmental component in the cause of stomach cancer.

Place of birth, which is sometimes used as a surrogate for ethnicity, may also be an indicator of elevated stomach cancer risks. Newman and Spengler showed that in comparison to Ontario men born in Canada, there are excesses of stomach cancer in Ontario residents born in Great Britain(SMR 159, CI 145-174), Italy (SMR 189, CI 155-228), The Netherlands(SMR 228, CICI 159-309), Poland (SMR 183, CI 151-222) and the Soviet Union(SMR 161, CI 131-196) (72). As Stock points out however, "the role of ethnicity is confusing....the risk of stomach cancer may be higher in immigrants who may have lower socioeconomic status, poorer diets and/or use coal for cooking and heating rather than due to ethnicity per se" (87).

However, several studies on the Ontario gold mining population have reported higher rates of stomach cancer among those born in Canada versus foreign born (63,83,44). In particular, Kusiak and colleagues report a statistically significant excess in both groups. When these groupings are further analyzed by age however, an interesting pattern becomes apparent. The excess of stomach cancer among foreign born miners over age 60 is similar to that seen throughout Ontario among those of similar ethnic background. The excess among all gold miners under age 60 is elevated regardless of place of birth.

iv) Conclusions

• Dietary factors may contribute to the elevated rates of stomach cancer in Northern Ontario but they cannot account for the elevated rates seen only among goldminers and not among other Northern Ontario miners.
• There is no clear or consistent evidence that cigarette smoking is associated with increased rates of stomach cancer. In any case, this could not explain the elevated rates seen only in goldminers, since their rates of smoking were no different from nickel/copper miners.
• The evidence linking stomach cancer with alcohol consumption is inconsistent. However, mortality data on the large cohort of miners listed in the Mining Master File indicates an unusually low rate of cirrhosis of the liver, implying that Ontario miners drink less than the average Ontario male.
• While place of birth affects stomach cancer rates, it can not account for the excess mortality seen among Ontario goldminers with latency under twenty years (Kusiak et al., 1993). It is conceivable that miners born outside North America may have been exposed to different mining conditions outside Canada which could have prolonged the period of latency beyond 20 years.

CHAPTER 3. SUMMARY OF CONCLUSIONS

1. WHAT IS THE EVIDENCE CONCERNING STOMACH CANCER MORTALITY AMONG NON GOLD MINERS WORLDWIDE AND IN ONTARIO?

• As cited in Figure 2, the evidence of an increase in the rates of stomach cancer among non-gold miners worldwide is inconsistent. However, the literature supports the potential work-relatedness of stomach cancer among certain occupational groups as described in the review by Susan Stock (87).
• There is no evidence of a statistically significant increase in stomach cancer mortality among non-goldminers in Ontario.

2. WHAT IS THE EVIDENCE CONCERNING STOMACH CANCER MORTALITY AMONG GOLDMINERS WORLDWIDE AND IN ONTARIO?

• All analyses of the Ontario cohort and two of three international studies report elevated rates of stomach cancer among goldminers.
• The highest SMRs for stomach cancer are observed in goldminers who began work in gold after 1945. However, as Kusiak et al. postulated and Tomlinson has confirmed, the differences in the cohort age structure pre and post 1945 are responsible for this artefact.
• Underascertainment problems due to absence of SINs in pre-1945 hires can account for only about 10% of the observed differences between pre and post 1945 SMRs.
• Differences in the cohort age structure pre and post 1945 have likely resulted in artefactual differences between SMRs.
• The increase in stomach cancer appears 5-19 years after first gold mining and peaks between 10 and 19 years, followed by an apparent decline.
• The Ontario studies consistently show that goldminers exhibit statistically significant elevated mortality rates for stomach cancer. The overall SMRs vary from 136 to 157, with the highest SMR reaching 463 among those with the highest time-weighted index of exposure to chromium and age less than 60.
• A dose response relationship has been established by Kusiak et al., 1993, for the time weighted duration of employment in gold mines for men under the age of 60, and in particular for the time-weighted exposure to chromium and/or dust. This relationship was not detected by Shannon,1987 or Miller, 1987, both of whom used duration of employment as a surrogate for exposure.
• There is strong evidence that goldminers under the age of 60 are at greater relative risk for stomach cancer than those over 60.
• The evidence consistently demonstrates that it is unlikely that place of birth is an important factor in the increased stomach cancer mortality among Ontario goldminers.
• An increase in the intestinal type of stomach cancer among younger miners may be a reason for the elevated rates of stomach cancer mortality within the 5 - 19 year window since first mining gold.

3. WHAT IS KNOWN ABOUT POTENTIAL OCCUPATIONAL CAUSES OF STOMACH CANCER?

• Numerous studies show statistically significant associations between a variety of occupations and stomach cancer.
• No specific occupational substance has been conclusively identified as the causal agent.
• Dusty work environments are known to be associated with elevated risk of stomach cancer. The action of dust particulates may be one of mechanical irritation or disruption to the mucosal lining, permitting acid/mechanical damage or cellular contact with carcinogens.
• There is strong experimental evidence to show an association between certain nitroso compounds and stomach cancer.

4. ARE ANY OF THESE AND OTHER POTENTIAL CAUSES RELEVANT IN THE ONTARIO GOLD MINING ENVIRONMENT?