Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. METHODS: Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. RESULTS: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. CONCLUSION: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

Esophageal cancer among black men in Washington, D.C. II. Role of nutrition.

A case-control study of esophageal cancer was conducted among the black male residents of Washington, D.C., to find reasons for the exceptionally high risk in this population. The next of kin of 120 esophageal cancer cases who died during 1975-77 and of 250 D.C. black males who died of other causes were interviewed. Five indicators of general nutritional status--fresh or frozen meat and fish consumption, dairy product and egg consumption, fruit and vegetable consumption, relative weight (wt/ht2), and number of meals eaten per day--were each significantly and inversely correlated with the relative risk of esophageal cancer. Associations with other food groups were not apparent. The least nourished third of the study population, defined by any of these five measures, was at twice the risk of the most nourished third. None of these associations was markedly reduced by controlling for ethanol consumption, the other major risk factor in this population; smoking; socioeconomic status; or the other nutrition measures. When the three food group consumption measures were combined into a single overall index of general nutritional status, the relative risk of esophageal cancer between extremes was 14. Estimates of the intake of vitamin A, carotene, vitamin C, thiamin, and riboflavin were inversely associated with relative risk; but each micronutrient index was less strongly associated with risk than were the broad food groups that provide most of the micronutrient. Thus no specific micronutrient deficiency was identified. Instead, generally poor nutrition was the major dietary predictor of risk and may partially explain the susceptibility of urban black men to esophageal cancer.

Esophageal cancer among black men in Washington, D.C. I. Alcohol, tobacco, and other risk factors.

A case-control study involving interviews with the next of kin or close friends of 120 black males who recently died of esophageal cancer and 250 similarly aged black males who died of other causes was undertaken to discover reasons for the exceptionally high mortality from this cancer in Washington, D.C. The age-adjusted annual death rate in Washington, D.C., for nonwhite males, 1970-75, was 28.6/100,000, far higher than the national rate of 12.4/100,000 and the rates in other metropolitan areas of the country. The major factor responsible for the excess was alcoholic beverage consumption, with an estimated 81% of the esophageal cancers attributed to its use; high use of alcoholic beverages was also found among the controls. The relative risk (RR) of esophageal cancer associated with use of alcoholic beverages was 6.4 (95% confidence interval=2.5, 16.4). The RR increased with amount of ethanol consumed and was highest among drinkers of hard liquor, although the risk was also elevated among consumers of wine and/or beer only. The RR associated with cigarette smoking was 1.9 (1.0, 3.5) when controls with smoking-related causes of death were excluded but declined to 1.5 (0.7, 3.0) when adjusted for ethanol consumption. Significant differences of approximately twofold were found between low and high levels of a) consumption of fresh or frozen meat and fish, fruits and vegetables, and dairy products and eggs and b) relative weight (wt/ht2). The inverse trends with these general measures of nutritional status were not explained by alcoholic beverage consumption or socioeconomic status as measured by educational level.

Proportion of breast cancer cases in the United States explained by well-established risk factors.

BACKGROUND: Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published. All estimates are based on selected groups, making their generalizability to the U.S. population uncertain. PURPOSE: Our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e., later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population. METHODS: From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey. RESULTS: Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population. CONCLUSIONS: The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors. IMPLICATIONS: Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention.

Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

The relationship between dietary fat intake and breast cancer incidence was examined in the National Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is derived from adults (greater than or equal to 25 yr) examined in the NHANES I (1970-75) cross-sectional survey of the U.S. population and provides a mean follow-up time of 10 years. An analytic sample of 5,485 women, including 99 breast cancer cases (34 premenopausal and 65 postmenopausal at NHANES I baseline), was examined for associations with dietary intake of fat, percent energy from fat, total energy, saturated fat, polyunsaturated fat, monounsaturated fat, and cholesterol on the basis of a 24-hour recall administered at the baseline NHANES I examination. No significant differences in dietary fat intake between cases and noncases were evident when mean intakes for each group were compared. For total fat (g) and saturated fat (g), a significant inverse association was indicated in proportional hazards analyses. Adjustment of fat for total energy intake resulted in a smaller effect that was no longer statistically significant. Adjustment for accepted breast cancer risk factors did not change these findings. This prospective study of a sample from the U.S. population does not support the hypothesis that high dietary fat intake increases breast cancer risk. Indeed, some lower risk associated with high fat intake may be indicated, although this result may be influenced by methodologic problems with the dietary assessment.

Dietary carotene and vitamin A and risk of lung cancer among white men in New Jersey.

A population-based incident case-control study of lung cancer in white males was conducted during 1980-81 in six high-risk areas of New Jersey. Interviews were completed with 763 cases and 900 controls or with their next of kin. In order to assess whether dietary intake of carotene, preformed retinol, or total vitamin A modified the risk of lung cancer, subjects were asked about their usual frequency of consumption, several years earlier, of 44 food items, which provides 83% of the vitamin A in the American diet, and about their use of vitamin supplements. The men in the lowest quartile of carotene intake had 1.3 the risk (P-value for trend = .05) of those in the highest quartile after adjustment was made for smoking duration and intensity and education. No association was seen for retinol (P-value for trend = .11) or total vitamin A (P-value for trend = .30). The inverse association between carotene intake and lung cancer was most compelling for squamous cell carcinoma, with the smoking-and education-adjusted risk of those in the lowest quartile reaching 1.4 (P-value for trend = .03) the risk of those men in the highest quartile. Risk of lung adenocarcinoma was not related to carotene intake. The reduction in risk of squamous cell lung cancer with increasing carotene intake was noted in pipe and cigar smokers and cigarette smokers of different intensities. Among nonsmokers adenocarcinoma predominated. The inverse association between carotene and risk of squamous cell lung cancer was not especially strong or graded in response; but it was consistent and could be noted in each stratum when the subjects were divided by education, age, or mode of interview (direct vs. next of kin). The results of the other 4 case-control and 3 cohort studies that have looked at diet and risk of lung cancer are not consistent, and the question whether dietary carotene or total vitamin A reduces the risk of lung cancer is not yet resolved.

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.

Relative weight, weight change, height, and breast cancer risk in Asian-American women.

BACKGROUND: Breast cancer incidence rates have historically been four to seven times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, their breast cancer risk rises over several generations and reaches that for white women in the United States, indicating that modifiable exposures are involved. In a previous report on this case-control study of breast cancer in Asian-American women, designed to take advantage of their diversity in risk and lifestyle, we demonstrated a sixfold gradient in risk by migration history, comparable to the international differences in breast cancer incidence rates. PURPOSE: In this analysis, we have examined the roles of adult height, adiposity, and weight change in breast cancer etiology. METHODS: A population-based, case-control study of breast cancer was conducted among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, living in San Francisco-Oakland (CA), Los Angeles (CA), and Oahu (HI) during the period from April 1, 1983, through June 30, 1987. We successfully interviewed 597 (70%) of 852 eligible case subjects and 966 (75%) of 1287 eligible control subjects from August 1985 through February 1989. Subjects were asked about current height, usual adult weight, and usual weight in each decade of life, excluding the most recent 3 years and any periods of pregnancy. RESULTS: Height, recent adiposity (weight in the current decade of life/height 1.5), and recent weight change (between the current and preceding decades of life) were strong predictors of breast cancer risk after adjustment was made for accepted breast cancer risk factors. Risk doubled (relative risk [RR] = 2.01; 95% confidence interval [CI] = 1.16-3.49) over the 7-inch (17.8-cm) range in height (two-sided P for trend = .003), with comparable effects in both premenopausal and postmenopausal women. Except for reduced risk in the heavy, younger women (weight/height 1.5 > 29 kg/m 1.5 and < 40 years old), risk was positively associated with usual adult adiposity. Trends in risk became more striking as adiposity in each succeeding decade of adult life was considered. Women in their 50s and in the top quintile for their age group had twice the breast cancer risk (RR = 2.13; 95% CI = 1.17-3.87) of women in the bottom quintile (two-sided P for trend = .004). Women in their 50s, above the median adiposity for their age group, and with a recent gain of more than 10 pounds had three times the risk (RR = 3.01; 95% CI = 1.45-6.25) of women below the median adiposity and with no recent weight change. Recent weight loss was consistently associated with reduced risk (RRs of approximately 0.7) relative to no recent weight change. CONCLUSIONS: Adult adiposity, weight change, and height are critical determinants of breast cancer risk. Increased adiposity and weight gain in the decade preceding diagnosis are especially influential, suggesting that excess weight may function as a late stage promoter. IMPLICATIONS: Weight maintenance and/or reduction as an adult, possibly accompanied by specific changes in diet and physical activity, may have a significant and rapid impact on breast cancer risk.

Migration patterns and breast cancer risk in Asian-American women.

BACKGROUND: Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites. PURPOSE: Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women. METHODS: A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%). RESULTS: A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate. CONCLUSIONS: Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life. IMPLICATIONS: Because heterogeneity in breast cancer risk in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer.

Does beta-carotene explain why reduced cancer risk is associated with vegetable and fruit intake?

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Breast cancer risk assessed by anthropometry in the NHANES I epidemiological follow-up study.

We examined the relation of anthropometric variables and breast cancer risk in the Epidemiological Follow-up Study of the first National Health and Nutrition Examination Survey, a cohort study based on a sample of the United States population. A total of 7149 women, 25 to 74 years of age, who were examined during the period 1971 through 1975 were included in the analysis. Stature, sitting height, elbow width, weight, and subscapular and triceps skinfold measurements were collected during the baseline interview and examination. Breast cancer cases (N = 121) were identified through hospital records or death certificates. The median follow-up period for this cohort was 10 years. Women who developed breast cancer were taller and had greater frame size (elbow width) than women who remained free of breast cancer during the follow-up period. After controlling for the effect of potential confounders, the relative risk of breast cancer was 1.9 (95% confidence interval, 1.1 to 3.1) and 2.2 (95% confidence interval, 1.3 to 3.8) among women in the fourth quartiles of stature and elbow width, respectively. Body size defined by weight, relative weight, or skinfold measurements was not associated with increased risk of breast cancer. The positive association of stature and frame size to risk of breast cancer suggests a potential role of early nutrition in cancer etiology.

Diet in the etiology of oral and pharyngeal cancer among women from the southern United States.

A case-control interview study involving 227 women in North Carolina with oral cavity or pharyngeal cancer and 405 matched controls showed a protective effect of a usual adult diet high in fruits and vegetables. The relative risks of 0.65 for moderate and 0.52 for high (relative to 1.0 for infrequent) consumption of fruits and vegetables were statistically significant and remained after controlling for demographic characteristics, tobacco and alcohol use, relative weight, and intake of other food groups. Risks were lower with higher bread and cereal intake but higher for those women with the lightest weights, adjusted for height. The inverse associations between oral and pharyngeal cancer and intake of fruits and vegetables and intake of breads and cereals could not be attributed to an association with general nutritional status, since meat and fish consumption was related to an increased risk of oral and pharynx cancer. Moreover, dairy and egg consumption was generally unrelated to cancer risk. The reduction in risk with greater fruit and vegetable consumption is consistent with the hypothesis that vitamin C and/or beta-carotene intake is associated with a reduced risk of oral and pharyngeal cancer.

Protocol for a study of nutritional factors and the low risk of colon cancer in Southern retirement areas.

Colon cancer shows a distinct geographic pattern in the United States, with mortality rates in the Northeast exceeding those in the South by about 50%. The North-South gradient remains even after adjustment for differences in urbanization and socioeconomic status. Those counties in the South that attract large numbers of retirees from the North retain the low colon mortality rates characteristic of the South, even at older ages. This observation implies either that certain life-style changes associated with migration at retirement rapidly reduce the risk of colon cancer or that individuals migrate selectively, based on some correlate of health. A specific hypothesis related to the former possibility is that consumption of fruits and vegetables, and the associated vitamin C, carotene, and fiber, is elevated in the South and related to the reduced risk of colon cancer. A protocol is presented for a case-control interview study in Southern retirement areas to assess these possible explanations. A detailed residential history, as well as information on frequency of consumption of specific foods, food groups, and micronutrients, will be collected by interview and will be complemented by selected serum micronutrient determinations and fecal mutagenicity assays.

Occupational risk factors for laryngeal cancer on the Texas Gulf Coast.

Analyses are reported from a case-control interview study of incident laryngeal cancer on the Gulf Coast of Texas. Study subjects were 183 white men with squamous cell carcinoma of the larynx and 250 frequency matched controls. Occupational exposures were examined controlling for potential confounding by cigarette smoking and alcohol consumption. Significantly elevated risks were seen for men employed in the public services industry [transportation, communication, utilities, sanitary service; relative risk (RR), 1.6]; in metal fabricating (RR, 2.1), construction (RR, 1.7), and maintenance (RR, 2.7) occupations; and for workers potentially exposed to paint (RR, 1.8) and diesel or gasoline fumes (RR, 1.5). Elevated risks of border-line significance were seen for men employed as woodworkers/furniture makers (RR, 8.1) and for those with occupational exposure to asbestos (RR, 1.5). When asbestos was categorized by intensity of exposure, a significant positive gradient was found.

Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

We studied the relation of total serum cholesterol to all cancer and site-specific cancer incidence in a cohort based on a probability sample of the United States population. A total of 5125 men (yielding 459 cancers) and 7363 women (398 cancers) were initially examined in 1971-75 and followed a median of 10 yr. An examination of age-adjusted incidence rates by cholesterol level showed an inverse association between cholesterol and all cancer; lung, colorectal, pancreatic, and bladder cancers; and leukemia. In women a weak inverse relation (reflecting an elevated rate among those only in the lowest cholesterol quintile) was apparent for all cancer; more prominent inverse associations were seen for cancers of the lung, pancreas, bladder, cervix, and for leukemia. A more detailed analysis of cholesterol and colorectal cancer revealed little association in both men and women. For an aggregate group of smoking-related cancers, the inverse relation was especially prominent: the multivariate relative risk estimates for subjects in the lowest cholesterol quintile, compared to those in the highest quintile, were 2.1 (1.1-3.8) and 3.3 (1.4-7.8) for men and women, respectively. The inverse association was present for smoking-related cancers diagnosed 6 or more yr after cholesterol determination in both men and women, suggesting that this association cannot be simply dismissed as a preclinical cancer effect. Further investigation of the cholesterol-cancer question, particularly the relation between cholesterol and smoking-related cancers, may provide useful etiological leads.

The relation of passive smoking to lung cancer.

To evaluate the role of passive smoking in the development of lung cancer among nonsmokers, data were pooled from three large incident case-control interview studies. Ninety-nine lung cancer cases and 736 controls never used any form of tobacco. Overall the adjusted odds ratio for lung cancer among nonsmokers ever living with a smoker was 0.8 (95% confidence interval, 0.5-1.3) rising to 1.2 among those exposed for 40 or more years. Persons living with a spouse who smoked cigarettes were at increased risk (adjusted odds ratio, 1.5; 95% confidence interval, 0.8-2.8). When adjusted for age and gender, there was a significant trend in risk with increasing amounts smoked per week by the spouse (P = 0.05) and with cumulative pack-years of exposure (P = 0.03). This effect was limited to females, especially older women whose husbands were heavy smokers. The elevated risk associated with spouse smoking was restricted to squamous and small cell carcinomas (odds ratio, 2.9; 95% confidence interval, 0.9-9.3), which provides additional evidence linking passive smoking to lung cancer.

Colorectal cancer in rural Nebraska.

A case-control interview study of colorectal cancer was conducted in two rural counties of eastern Nebraska to determine reasons for the elevated colon cancer mortality rates during 1950 to 1969. Comparison of the information provided by 86 colorectal cancer cases and 176 matched controls (or their next of kin) revealed an increased risk among persons of Czech background, with persons of Bohemian and Moravian extraction predominating in this area. The data suggest an interaction between Bohemian ancestry and certain dietary patterns in the pathogenesis of colon cancer in this region. Colon cancer risk was elevated among commercial beer drinkers regardless of their ethnic background, although Bohemians reported heavier consumption. An excess risk was also associated with intestinal polyps, reported more often by Moravians, and with familial occurrence of gastrointestinal and other cancers. Since 1969, the mortality and incidence rates for colon cancer in this area have declined, possibly as a consequence of acculturation of the American-born descendants of Czech immigrants.