Autoimmune thyroiditis and exposure to iodine 131 in the Ukrainian cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: results from the first screening cycle (1998-2000).

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

A follow-up study of a ten-percent sample of the Canadian labor force. I. Cancer mortality in males, 1965-73.

A system is described for monitoring the mortality experience of an approximately 10% sample of the Canadian Labor Force with the use of computerized record linkage to the Canadian mortality data base. Results are presented for the 4,203 cancer deaths that occurred between 1965 and 1973 in 415,201 males with known occupational histories from 1965 to 1969. A number of previously suggested associations between certain occupations and cancers have been confirmed in these results, and a number of new associations also have been observed. The system provides a powerful tool for both generating and testing hypotheses, and this power will increase as further mortality experience is accumulated by the cohort.

Age at first pregnancy and risk of colorectal cancer: a case-control study.

Results from a case-control study of colorectal cancer conducted in Toronto and Calgary, Canada, are reported with respect to pregnancy-related variables. A total of 158 female "ever-married" colon cancer cases, 71 rectum cancer cases, 242 neighborhood controls, and 257 hospital controls were interviewed to obtain a complete pregnancy history. The results indicate a strong protective effect of early age at first pregnancy for both colon and rectum cancers, with little or no effect noted for the total number of pregnancies. There is a suggestion that age at first pregnancy may have a greater effect on right colon cancer than on left colon cancer. In addition, there also is a suggestion that non-live-birth outcomes may be a risk factor for both colon and rectum cancer. The similarity of these results to those of other studies on large bowel cancer and on breast cancer support the hypothesis that carcinogenesis in the large bowel may be at least partly mediated by female sex hormones.

Correlations between cancer incidence rates from the Canadian National Cancer Incidence Reporting System, 1969-78.

Incidence rates for 19 cancers in females and 16 cancers in males have been computed from data reported by 8 Canadian provinces to the National Cancer Incidence Reporting System between 1969 and 1978. The rates, very similar in absolute and relative magnitude to those reported by the U.S. Third National Cancer Survey, have been used to examine patterns of correlation between various cancers within the 8 provinces. There is strong evidence of positive associations between a number of cancers, including a number of associations that have been reported in other similar correlational studies. Correlations that may be of particular interest in suggesting etiologic factors in common include clusters of smoking-related cancers (buccal cavity with pharynx, larynx, lung, and bladder), female sexual cancers (breast, corpus uteri, and ovary), and a group of cancers that have shown correlation in other studies (i.e., cancers of the pancreas and kidney, leukemias, lymphomas, and cancer of the prostate gland). Organs in the gastrointestinal tract (esophagus, stomach, colon, and rectum) anatomically close to each other show a high positive correlation in both females and males, but the further apart the organs are the lower is the correlation; these observations are consistent with other evidence of varying dietary etiologies. Two individual correlations of particular interest are those between female brain tumors and female bladder cancer (two cancers for which little is known of the etiology for a large percentage of them) and those between female breast cancer and female lung cancer. This study, the largest correlational study of incidence data reported to date, demonstrates the utility of such simple correlational analyses.

A cohort study of fat intake and risk of breast cancer.

Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients. There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052).

Tobacco, alcohol, asbestos, and nickel in the etiology of cancer of the larynx: a case-control study.

A case-control study of laryngeal cancer was conducted in southern Ontario between 1977 and 1979 with 204 subjects with newly diagnosed cancer and 204 controls, individually matched by sex, age, and residence. Tobacco products and alcohol showed strong associations with cancer of the larynx for males, with relative risks (RR) for users of cigarettes, cigars or cigarillos, pipes, and alcohol of 6.1, 2.9, 1.6, and 5.2, respectively. The population attributable risk percent for males using tobacco products and alcohol together was estimated to be 94%. Cigarette smoking was also an important risk factor for females, although the small number of female pairs (20) precluded any meaningful detailed analysis of other possible risk factors. The RR for males for exposure to asbestos after the effects of cigarette smoking were controlled was 2.3, and the effects seemed restricted to cigarette smokers. The findings on asbestos were based on small numbers of cases and controls exposed and consequently were subject to large sampling errors. The estimate was consistent, however, with that from other studies and supported a causal role for asbestos exposure and cancer of the larynx. The RR for males for exposure to nickel was 0.9.

Dietary fat intake and risk of epithelial ovarian cancer.

BACKGROUND: Evidence exists that dietary fat may be a contributory factor in the development of hormone-related cancers such as ovarian cancer. Previous studies have demonstrated significantly higher circulating-estrogen levels among nonvegetarian women than among vegetarian women; the increase correlated directly with consumption of saturated fat. However, the contribution that dietary fat plays in the development of hormone-related cancers remains unresolved. PURPOSE: Our purpose was to evaluate whether saturated fat intake increases the risk of ovarian cancer development. METHODS: Population-based sampling was used to acquire cases and controls over a 3-year period from the study area, which included the highly populated region surrounding the western end of Lake Ontario, Canada. From the Ontario Cancer Registry, all histologically confirmed, primary malignant or borderline malignant epithelial ovarian tumors first diagnosed from November 1989 through October 1992 among study-area residents aged 35-79 years were determined. In total, 631 eligible case subjects were identified, of whom 450 (71.3%) were interviewed concerning reproduction and diet; 564 randomly selected population control subjects were similarly interviewed. From the quantitative diet-history information, average daily intakes of macronutrients and micronutrients were calculated. Unconditional continuous logistic regression methods were used for analysis, with adjustment for age at interview, number of full-term pregnancies, years of oral contraceptive use, and total daily caloric intake. RESULTS: Saturated fat consumption was associated with increasing risk of ovarian cancer (odds ratio [OR] = 1.20 for each 10 g/day of intake; 95% confidence interval [CI] = 1.03-1.40; one-sided P = .0082). No relationship was seen with intake of unsaturated fats. Egg consumption also appeared related to increased risk (OR = 1.42 for each 100 mg of egg cholesterol per day; 95% CI = 1.18-1.72; two-sided P = .0002), though this association may have resulted from disease-related changes in the dietary practices of case subjects prior to diagnosis. Consumption of vegetable fiber (but not fruit or cereal fiber) was associated with decreased risk (OR = 0.63 for each 10 g/day; 95% CI = 0.49-0.80; two-sided P = .0001). All three nutrients (saturated fat, egg cholesterol, and vegetable fiber) remained statistically significant when included in the same regression model. CONCLUSION: Diet may contribute to risk of ovarian cancer development. IMPLICATION: If confirmed in further studies, this association may allow women to appreciably lower their risk of ovarian cancer through dietary modifications: reducing the intake of saturated fats and eating more vegetables.

Cancer mortality (1965-77) in relation to diesel fume and coal exposure in a cohort of retired railway workers.

A cohort study of 43,826 male pensioners of the Canadian National Railway Company was conducted. The cause of death of 17,838 pensioners who died between 1965 and 1977 was ascertained by computerized record linkage to the Canadian national mortality data base. The main finding was an elevated risk of lung cancer for those employed in occupations involving exposure to diesel fumes and coal dust, with highly significant dose-response relationships observed. That such association may be due in part to smoking cannot be excluded; but in view of the widespread exposure to diesel fumes, the finding warrants further investigation. The present study also demonstrated the utility and feasibility of large-scale occupational cohort studies conducted with the use of computerized record linkage to national mortality records.

Lung cancer mortality (1950-80) in relation to radon daughter exposure in a cohort of workers at the Eldorado Beaverlodge uranium mine.

A cohort study of 8,487 workers employed between 1948 and 1980 at a uranium mine in Saskatchewan, Canada, has been conducted. A total of 65 lung cancer deaths was observed (34.24 expected, P less than 10(-5)). There was a highly significant linear relationship between dose and increased risk of lung cancer giving estimates for the relative and attributable risk coefficients of 3.28% per working level month (WLM) and 20.8 per WLM per 10(6) person-years. Age at first exposure had a significant modifying effect on risk. The interaction of exposure with age at observation fits a relative risk model well. The similarity of these results to a recent study of Swedish iron miners with similar levels of relatively low exposure suggests that exposure to radon daughter products may be a major contributory factor to lung cancer occurring among nonsmokers in the general population. The results also reinforce concerns as to the appropriateness of present occupational exposure standards.

Tobacco use, occupation, coffee, various nutrients, and bladder cancer.

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.

Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies.

BACKGROUND: Exposure to the radioactive gas radon and its progeny (222Rn and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. PURPOSE: This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. METHODS: Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64,209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. RESULTS: For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than 10 years since the start of employment, for other and unspecified cancers (excess relative risk per WLM = 0.22%; 95% CI = 0.08-0.37). CONCLUSIONS: The increases in mortality from stomach and liver cancers and leukemia are unlikely to have been caused by radon, since they are unrelated to cumulative exposure. The association between cumulative exposure and pancreatic cancer seems likely to be a chance finding, while the association between cumulative exposure and other and unspecified cancers was caused by deaths certified as due to carcinomatosis (widespread disseminated cancer throughout the body) that were likely to have been due to lung cancers. This study, therefore, provides considerable evidence that high concentrations of radon in air do not cause a material risk of mortality from cancers other than lung cancer. IMPLICATIONS: Protection standards for radon should continue to be based on consideration of the lung cancer risk alone.

Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies.

BACKGROUND: Colorectal cancer is a major public health problem in both North America and western Europe, and incidence and mortality rates are rapidly increasing in many previously low-risk countries. It has been hypothesized that increased intakes of fiber, vitamin C, and beta carotene could decrease the risk of colorectal cancer. PURPOSE: The objective of this study was to examine the effects of fiber, vitamin C, and beta-carotene intakes on colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. The study was designed to estimate risks in the pooled data, to test the consistency of the associations across the studies, and to examine interactions of the effects of the nutrients with cancer site, sex, and age. METHODS: Original data records for 5287 case subjects with colorectal cancer and 10,470 control subjects without disease were combined. Logistic regression analysis was used to estimate relative risks and confidence intervals for intakes of fiber, vitamin C, and beta carotene, with the effects of study, sex, and age group being adjusted by stratification. RESULTS: Risk decreased as fiber intake increased; relative risks were 0.79, 0.69, 0.63, and 0.53 for the four highest quintiles of intake compared with the lowest quintile (trend, P < .0001). The inverse association with fiber is seen in 12 of the 13 studies and is similar in magnitude for left- and right-sided colon and rectal cancers, for men and for women, and for different age groups. In contrast, after adjustment for fiber intake, only weak inverse associations are seen for the intakes of vitamin C and beta carotene. CONCLUSION: This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum. IMPLICATIONS: If causality is assumed, we estimate that risk of colorectal cancer in the U.S. population could be reduced about 31% (50,000 cases annually) by an average increase in fiber intake from food sources of about 13 g/d, corresponding to an average increase of about 70%.

Lung cancer mortality (1950-80) in relation to radon daughter exposure in a cohort of workers at the Eldorado Port Radium uranium mine: possible modification of risk by exposure rate.

A cohort study of 2,103 workers employed between 1942 and 1960 at a uranium mine in the Northwest Territories, Canada, was conducted. A total of 57 lung cancer deaths was observed (expected = 24.73, P less than .0001). There was a highly significant linear relationship between exposure and increased risk of lung cancer, giving estimates for the relative and attributable risk coefficients of 0.27 per working level month (WLM) and 3.10 per WLM per 10(6) person-years. These risk coefficients were substantially less than those estimated from the experience of miners in the Beaverlodge mine, which have previously been reported. Any biases in the present estimates are likely to have been upward, and therefore they probably represent an upper limit. The major difference between the two mine cohorts is in the exposure rate, since the Port Radium miners were exposed to much greater concentrations of radon daughters than the Beaverlodge miners. It is postulated that risk of lung cancer from radon daughter exposure may be modified by exposure rate, for which hypothesis there is some support from other epidemiologic data.

An exploratory case-control study of brain tumors in adults.

An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies.

We conducted a combined analysis of the original data to evaluate the consistency of 12 case-control studies of diet and breast cancer. Our analysis shows a consistent, statistically significant, positive association between breast cancer risk and saturated fat intake in postmenopausal women (relative risk for highest vs. lowest quintile, 1.46; P less than .0001). A consistent protective effect for a number of markers of fruit and vegetable intake was demonstrated; vitamin C intake had the most consistent and statistically significant inverse association with breast cancer risk (relative risk for highest vs. lowest quintile, 0.69; P less than .0001). If these dietary associations represent causality, the attributable risk (i.e., the percentage of breast cancers that might be prevented by dietary modification) in the North American population is estimated to be 24% for postmenopausal women and 16% for premenopausal women.

Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

BACKGROUND: International and interethnic differences in prostate cancer incidence suggest an environmental, potentially modifiable etiology for the disease. PURPOSE: We conducted a population-based case-control study of prostate cancer among blacks (very high risk), whites (high risk), and Asian-Americans (low risk) in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto. Our aim was to evaluate the roles of diet, physical activity patterns, body size, and migration characteristics on risk in these ethnic groups and to assess how much of the interethnic differences in risk might be attributed to interethnic differences in such lifestyle characteristics. METHODS: We used a common protocol and questionnaire to administer personal interviews to 1655 black, white, Chinese-American, and Japanese-American case patients diagnosed during 1987-1991 with histologically confirmed prostate carcinoma and to 1645 population-based control subjects matched to case patients by age, ethnicity, and region of residence. Sera collected from 1127 control subjects were analyzed for levels of prostate-specific antigen (PSA) to permit comparison of case patients with control subjects lacking serological evidence of prostate disease. Odds ratios were estimated using conditional logistic regression. We estimated the proportion of prostate cancer attributable to certain risk factors and the proportion of interethnic risk differences attributable to interethnic differences in risk-factor prevalence. RESULTS: A positive statistically significant association of prostate cancer risk and total fat intake was found for all ethnic groups combined. This association was attributable to energy from saturated fats; after adjusting for saturated fat, risk was associated only weakly with monounsaturated fat and was unrelated to protein, carbohydrate, polyunsaturated fat, and total food energy. Saturated fat intake was associated with higher risks for Asian-Americans than for blacks and whites. In all ethnic groups combined, the risk tended to be higher when only case patients with advanced disease were compared with control subjects with normal PSA levels. Among foreign-born Asian-Americans, risk increased independently with years of residence in North America and with saturated fat intake. Crude estimates suggest that differences in saturated fat intake account for about 10% of black-white differences and about 15% of white-Asian-American differences in prostate cancer incidence. Risk was not consistently associated with intake of any micronutrients, body mass, or physical activity patterns. CONCLUSIONS: These data support a causal role in prostate cancer for saturated fat intake but suggest that other factors are largely responsible for interethnic differences in risk.

Vasectomy and prostate cancer: results from a multiethnic case-control study.

BACKGROUND: Vasectomy, a widely used form of contraception, has been associated in some studies with increased prostate cancer risk. PURPOSE: We assessed this association on the basis of data collected in a large multiethnic case-control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). METHODS: In home interviews conducted with newly diagnosed prostate cancer case patients and population control subjects, we obtained information on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed, as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of sex hormones and sex hormone-binding globulin. RESULTS: The present analysis was based on 1642 prostate cancer patients and 1636 control subjects. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.83-1.3), whites (OR = 0.94; 95% CI = 0.69-1.3), blacks (OR = 1.0; 95% CI = 0.59-1.8), or Chinese-Americans (OR = 0.96; 95% CI = 0.42-2.2). Among Japanese-Americans, the OR was 1.8 (95% CI = 0.97-3.4), but the statistically nonsignificant elevation in risk was limited to more educated men and those with localized cancers. ORs did not vary significantly by age at vasectomy or years since vasectomy. We found a lower serum concentration of sex hormone-binding globulin and a higher ratio of dihydrotestosterone to testosterone among vasectomized control subjects than among nonvasectomized control subjects. CONCLUSIONS: The findings of this study do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects seen in this cross-sectional comparison warrant further evaluation in longitudinal studies.

PIP: Vasectomy has been associated in some studies with increased prostate cancer risk. This association was assessed on the basis of data collected in a large multiethnic case control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). In home interviews conducted with newly diagnosed prostate cancer case patients (diagnosed between January 1, 1989 and December 31, 1991 as well as January 1, 1987 and December 31, 1988) and control subjects, information was obtained on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of total testosterone, percent of free testosterone, percent of bioavailable testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) using an automated, polyclonal-monoclonal immunochemiluminometric prostate-specific antigen (PSA) assay. The analysis was based on 1642 prostate cancer patients and 1636 control subjects. The analysis of PSA, androgens, and SHBG by vasectomy status was based on 850 control subjects with normal PSA concentrations. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; Whites OR = 0.94; Blacks OR = 1.0; or Chinese-Americans OR = 0.96). Among Japanese-Americans, the OR was 1.8, but the statistically significant elevation in risk (OR = 4.1) was limited to more educated men with a history of vasectomy and those with localized cancers (OR = 5.3). ORs did not vary significantly by age at vasectomy or years since vasectomy. Lower serum concentration of SHBG and a higher ratio of DHT to testosterone was found among vasectomized control subjects than among nonvasectomized control subjects. The findings do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects warrant further evaluation in longitudinal studies.

Lung cancer in radon-exposed miners and estimation of risk from indoor exposure.

BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.

Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.

BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. METHODS: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. RESULTS: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. CONCLUSIONS: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

Some methodological issues in epidemiological studies of fat and cancer.

Three types of approach to the study of the possible relationship between fat and cancer are discussed, namely, correlational, case-control, and cohort studies. The advantages and limitations of each method are analyzed, and it is emphasized that a necessary prerequisite to direct observational studies in humans is the development of a satisfactory and uniform method of a diet assessment. Despite the problems, epidemiological research in this area offers considerable potential for cancer prevention.