Cigarette smoking,use of other tobacco products and stomach cancer mortality in US adults: The Cancer Prevention Study II

Cigarette smoking is associated with increased risk of stomach cancer in many studies but there are limited data on this relationship in women and on risk associated with use of tobacco products other than cigarettes. We examined stomach cancer death rates in relation to cigarette smoking in women and use of cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective mortality study in the United States (US). Cohort follow-up from 1982-96 identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women, respectively. Cox proportional hazards models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent group. Multivariate-adjusted RRs were the highest for men who currently smoked cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75-2.67) and both increased with smoking duration. Women who currently (RR = 1.49, 95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes were at significantly increased risk, as were men who formerly smoked cigarettes (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men who reported a history of chronic indigestion or gastroduodenal ulcer had substantially higher mortality rates associated with current cigarette (RR = 3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as did men who were current aspirin users. If causal, the estimated proportion of stomach cancer deaths attributable to tobacco use would be 28% in US men and 14% in women. We conclude that prolonged use of tobacco products is associated with increased stomach cancer mortality in men and women. The accumulated evidence from this and other studies support reconsidering stomach cancer as a tobacco-related cancer.     

Cigar smoking in men and risk of death from tobacco-related cancers

BACKGROUND: Cigar consumption in the United States has increased dramatically since 1993, yet there are limited prospective data on the risk of cancer associated with cigar smoking. We examined the association between cigar smoking and death from tobacco-related cancers in a large, prospective cohort of U. S. men. METHODS: We used Cox proportional hazards models to analyze the relationship between cigar smoking at baseline in 1982 and mortality from cancers of the lung, oral cavity/pharynx, larynx, esophagus, bladder, and pancreas over 12 years of follow-up of the American Cancer Society's Cancer Prevention Study II cohort. A total of 137 243 men were included in the final analysis. Women were not included because we had no data on their cigar use. We excluded men who ever smoked cigarettes or pipes and adjusted all rate ratio (RR) estimates for age, alcohol use, and use of snuff or chewing tobacco. RESULTS: Current cigar smoking at baseline, as compared with never smoking, was associated with an increased risk of death from cancers of the lung (RR = 5.1; 95% confidence interval [CI] = 4.0-6.6), oral cavity/pharynx (RR = 4.0 [95% CI = 1.5-10.3]), larynx (RR = 10.3 [95% CI = 2.6-41.0]), and esophagus (RR = 1.8; 95% CI = 0.9-3.7). Although current cigar smokers overall did not appear to be at an increased risk of death from cancer of the pancreas (RR = 1.3; 95% CI = 0.9-1.9) or bladder (RR = 1.0; 95% CI = 0.4-2.3), there was an increased risk for current cigar smokers who reported that they inhaled the smoke (for pancreas, RR = 2.7; 95% CI = 1.5-4.8; for bladder, RR = 3.6; 95% CI = 1.3-9.9). CONCLUSIONS: Results from this large prospective study support a strong association between cigar smoking and mortality from several types of cancer.     

Family history and the risk of stomach cancer death in Japan: differences by age and gender.

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow-up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first-degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11-2.31) and women (RR 2.47; 95% CI 1.50-4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40-59 (RR 2.62; 95% CI 1.34-5.11 for men and RR 5.88; 95% CI 2.70-12.82 for women) than in the age group from 60-79 (RR 1.31; 95% CI 0.84-2.05 for men and RR 1.44; 95% CI 0.72-2.88 for women). In the age group from 40-59, men with father's history and women with mother's and sister's history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51-6.55, RR 10.46; 95% CI 4.54-24.12, RR 13.39; 95% CI 3.89-46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46-20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender-influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility.     

Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 incident cases of RCC. Relative risks were calculated using Cox regression, stratified by age and study center and adjusted for smoking status, education, alcohol consumption, physical activity, menopausal status, and hormone replacement therapy use. Among women, an increased risk of RCC was conferred by body weight (relative risk [RR] in highest vs. lowest quintile = 2.13; 95% confidence interval [CI] = 1.16-3.90; p-trend = 0.003), body mass index (BMI) (RR = 2.25; 95% CI = 1.14-4.44; p-trend = 0.009), and waist (RR = 1.67; 95% CI = 0.94-2.98; p-trend = 0.003) and hip circumference (RR = 2.30; 95% CI = 1.22-4.34; p-trend = 0.01); however, waist and hip circumference were no longer significant after controlling for body weight. Among men, hip circumference (RR = 0.44; 95% CI = 0.20-0.98; p-trend = 0.03) was related significantly to decreased RCC risk only after accounting for body weight. Height was not related significantly to RCC risk. Our findings suggest that obesity is related to increased risk of RCC irrespective of fat distribution among women, whereas low hip circumference is related to increased RCC risk among men. Our data give further credence to public health efforts aiming to reduce the prevalence of obesity to prevent RCC, in addition to other chronic diseases.     

Cancer Incidence in BRCA1 mutation carriers

BACKGROUND: Germline BRCA1 mutations confer a substantial lifetime risk of breast and ovarian cancer, but whether cancer at other sites is increased is less clear. To evaluate the risks of other cancers in BRCA1 mutation carriers, we conducted a cohort study of 11 847 individuals from 699 families segregating a BRCA1 mutation that were ascertained in 30 centers across Europe and North America. METHODS: The observed cancer incidence was compared with the expected cancer incidence based on population cancer rates. Relative risks (RRs) of each cancer type in BRCA1 carriers relative to risks for the general population were estimated by weighting individuals according to their estimated probability of being a mutation carrier. All statistical tests were two-sided. RESULTS: BRCA1 mutation carriers were at a statistically significantly increased risk for several cancers, including pancreatic cancer (RR = 2.26, 95% confidence interval [CI] = 1.26 to 4.06, P =.004) and cancer of the uterine body and cervix (uterine body RR = 2.65, 95% CI = 1.69 to 4.16, P<.001; cervix RR = 3.72, 95% CI = 2.26 to 6.10, P<.001). There was some evidence of an elevated risk of prostate cancer in mutation carriers younger than 65 years old (RR = 1.82, 95% CI = 1.01 to 3.29, P =.05) but not in those 65 years old or older (RR = 0.84, 95% CI = 0.53 to 1.33, P =.45). Overall, increases in the risk for cancer at sites other than the breast or ovary were small and evident in women (RR = 2.30, 95% CI = 1.93 to 2.75, P =.001) but not in men (RR = 0.95, 95% CI = 0.81 to 1.12, P =.58). CONCLUSIONS: In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men. BRCA1 mutations may confer increased risks of other abdominal cancers in women and increased risks of pancreatic cancer in men and women.     

A prospective study of diet and stomach cancer mortality in United States men and women.

Frequent consumption of fruits, vegetables, and whole grains has been associated with a reduced risk of stomach cancer in the majority of case-control studies of these factors: however, prospective studies have been less consistent. We examined the association between selected major food groups (citrus fruits, vegetables, whole grains, and processed meats) and risk of fatal stomach cancer in the Cancer Prevention Study (CPS) II cohort of 1.2 million United States men and women. During 14 years of follow-up, we documented 439 stomach cancer deaths in women and 910 in men after exclusion of individuals with prevalent cancers, inadequate diet information, and recent weight loss at baseline in 1982. After controlling for other risk factors, none of the food groups examined were associated with risk of stomach cancer except for an unexpected increased risk with vegetable consumption in women [relative risk (RR) = 1.25; 95% confidence interval (CI), 0.99-1.58; highest versus lowest tertile, P = 0.06 for trend]. A high overall plant food intake (a sum of vegetables, citrus fruit, and whole grains) was associated with reduced risk in men (RR = 0.79; 95% CI, 0.67-0.93; highest versus lowest tertile, P = 0.003 for trend), but not in women (RR = 1.18; 95% CI, 0.93-1.50; P = 0.16 for trend). Of individual foods examined, liver consumption greater than twice/week was associated with an increased risk of fatal stomach cancer in women (RR = 1.96; 95% CI, 1.09-3.53) and men (RR = 1.63; 95% CI, 1.02-2.62) compared with nonconsumers. This study supports a modest role for plant foods in reducing the risk of fatal stomach cancer in men, but not in women.     

A prospective study of stomach cancer among a rural Japanese population: a 6-year survey.

Stomach cancer mortality was prospectively studied among 9753 Japanese men and women who first responded to a mailed questionnaire in 1985 and were then followed through May 31, 1991. During this follow-up period, 57 stomach cancer deaths were identified. Current smokers had an increased risk of deaths from stomach cancer compared with never smokers (relative risk (RR) = 2.29, 95% confidence interval (CI): 1.15-4.56), but there was no dose-response to amount of cigarettes smoked. Daily alcohol drinkers who consumed 50 ml or more of alcohol per day also had a greater risk than nondrinkers (RR = 3.05, 95% CI: 1.35-6.91). There was no association between stomach cancer mortality and individual food consumption except a positive association with fruit intake. However, frequent use (greater than or equal to 3-4/week) of broiling of meats and traditional style Japanese salad preparation in their cooking procedures were positively associated with stomach cancer mortality. The RR values compared with infrequent use (less than or equal to 1-2/month) were 2.27 (95% CI: 1.06-4.85) and 3.10 (95% CI: 1.40-6.85), respectively. A positive family history of cancer, especially stomach cancer, significantly increased the risk of stomach cancer deaths (RR = 2.01, 95% CI: 1.12-3.63). The effects of these variables remained after adjustment for other variables.     

Prospective study of three major dietary patterns and risk of gastric cancer in Japan

Dietary pattern analysis is an alternative and complementary approach to identify the relationship between diet and the risk of chronic disease. This study was aimed at investigating the associations between dietary patterns and the risk of gastric cancer in Japan. Using baseline data from a prospective study of 20,300 men and 21,812 women, we conducted factor analysis and identified 3 major dietary patterns, healthy, traditional and Western, and calculated the factor scores of each pattern for individuals. During 10 years of follow-up, 400 cases of gastric cancer were identified. We found an inverse association between the healthy pattern and gastric cancer risk in women [rate ratio for highest quartile (RR) = 0.56; 95% CI = 0.32-0.96; p for trend = 0.03], but not in men. In contrast, the traditional pattern was significantly associated with the increased risk of gastric cancer in both genders (for men, RR = 2.88, 95% CI = 1.76-4.72; for women, RR = 2.40, 95% CI = 1.32-4.35). The Western pattern was not associated with risk. These associations persisted in histologic subtypes. Our findings support the idea that the healthy pattern decreased the risk of gastric cancer among females, while the traditional pattern increased the risk in both genders.     

Prospective study of alcohol consumption and breast cancer risk in Japanese women

Epidemiologic evidence is lacking for the association between alcohol consumption and the risk of breast cancer in Japanese women. We addressed this association in a prospective cohort study with an average follow-up of 7.6 years. At baseline (1988-1990), cohort participants completed a self-administered questionnaire that included alcohol use, reproductive history and hormone use. The women were followed up for breast cancer incidence through December 31, 1997. Cox proportional hazards models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer incidence and any association with alcohol consumption. During a follow-up of 271,412 person-years, we identified 151 women with breast cancer, of whom 45 were current drinkers and 11 drank > or =15 g of alcohol/day. After adjustment for age and other potential risk factors for breast cancer, the RR for current drinkers was 1.27 (95% CI 0.87-1.84) compared to nondrinkers. Average alcohol intake of <15 g/day did not significantly increase the risk for breast cancer. However, risk was significantly increased for women who consumed > or =15 g/day of alcohol (RR = 2.93, 95% CI 1.55-5.54). Age at starting drinking and frequency of consumption per week were not significantly associated with breast cancer risk. Our cohort study demonstrated that Japanese women who consume at least a moderate amount of alcohol have an increased risk of breast cancer.     

Risk factors for oesophageal,lung, oral and laryngeal cancers in black South Africans

The authors used data collected from 1995 to 1999, from an on-going cancer case-control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5-4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6-204.6) for lung cancer in women, and 23.9 (95% CI 9.5-60.3) for lung cancer and 23.6 (95% CI 4.6-121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7-46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1-7.5) in men working in 'potentially noxious' industries. 'Frequent' alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0-2.9, for women and odds ratio=1.8, 95% CI 1.2-2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8-7.9 in males and odds ratio=4.8, 95% CI 3.2-6.1 in females). The above results are broadly in line with international findings.     

A Prospective Study of Stomach Cancer among a Rural Japanese Population: A 6-Year Survey

Stomach cancer mortality was prospectively studied among 9753 Japanese men and women who first responded to a mailed questionnaire in 1985 and were then followed through May 31, 1991. During this follow-up period, 57 stomach cancer deaths were identified. Current smokers had an increased risk of deaths from stomach cancer compared with never smokers (relative risk (RR) = 2.29, 95% confidence interval (CI): 1.15–4.56), but there was no dose-response to amount of cigarettes smoked. Daily alcohol drinkers who consumed 50 ml or more of alcohol per day also had a greater risk than nondrinkers (RR = 3.05, 95% CI: 1.35–6.91). There was no association between stomach cancer mortality and individual food consumption except a positive association with fruit intake. However, frequent use (≤3–4/week) of broiling of meats and traditional style Japanese salad preparation in their cooking procedures were positively associated with stomach cacer mortality. The RR values compared with infrequent use (≥1–2/month) were 2.27 (95% CI: 1–06–4.85) and 3.10 (95% CI: 1.40–6.85), respectively. A positive family history of cancer, especially stomach cancer, significantly increased the risk of stomach cancer deaths (RR=2.01, 95% CI: 1.12–3.63). The effects of these variables remained after adjustment for other variables.     

Height and Body Mass Index in Relation to Esophageal Cancer; 23-year Follow-up of Two Million Norwegian Men and Women

Objective: Associations between body mass index (BMI) and stature and cancers at different sites have been explored in a number of studies. For esophageal cancer there seems to be different effects of BMI for different histological subtypes. We explored these relations in a Norwegian cohort. Material and methods: Height and weight were measured in 2 million Norwegians during 1963-2001. Duringfollow-up, 2245 histologically verified esophageal cancer cases were registered. Relative risks (RR) of esophageal cancer were estimated using proportional Cox regression. Results: Compared with normal weighted (BMI 18.5-24.9 kg/m²) an increased risk of esophageal adenocarcinoma (OA) was observed in overweight men (BMI 25-29 kg/m²): RR=1.80 (95% CI: 1.48-2.19) and in obese men (BMI 30kg/m²): RR=2.58 (95% CI: 1.81-3.68). The corresponding risk estimates for women were RR=1.64 (95% CI: 1.08-2.49) and RR=2.06 (95% CI: 1.25-3.39). The opposite relation was observed for esophageal squamous cell carcinoma (OSCC). For overweight men the RR of OSCC was 0.72 (95% CI: 0.63-0.82) and 0.68 (95% CI: 0.50-0.93) for obese. The corresponding RR estimates for women were 0.52 (95% CI: 0.42-0.65) and 0.43 (95% CI: 0.32-0.59). In addition, the lowest men had the highest risk of esophageal cancer in general. Adjustment for smoking did not change these relations. Conclusion: BMI had opposite relations to the two most common histological groups of esophageal cancer. While low BMI increased the risk of OSCC, high BMI increased the risk of OA. An increased risk of esophageal cancer was found in the lowest men.     

A prospective study of waist circumference and body mass index in relation to colorectal cancer incidence

OBJECTIVES: To study the association between waist circumference and colorectal cancer, and whether it is independent of body mass index (BMI). METHODS: Between 1997 and 2005, 953 incident colorectal cancer cases (546 men and 407 women) were identified among 95,151 participants (44,068 men and 51,083 women) from the Cancer Prevention Study-II Nutrition Cohort. RESULTS: Waist circumference was associated with increased colorectal cancer incidence in both men (multivariable adjusted rate ratio (RR) 1.68, 95% confidence interval (CI) 1.12-2.53 for waist circumference > or =120 cm compared to <95 cm, p trend = 0.006) and women (RR 1.75, 95% CI 1.20-2.54 for > or =110 compared to <85 cm, p trend = 0.003). High levels of BMI were also associated with increased risk. After adjustment for BMI, waist circumference remained associated with a nonstatistically significant increase in colorectal cancer incidence in both men (RR 1.41, 95% CI 0.81-2.45 for > or =120 compared to <95 cm, p trend = 0.10) and women (RR 1.48, 95% CI 0.89-2.48 for > or =110 compared to <85 cm, p trend = 0.13). CONCLUSIONS: Our results confirm that waist circumference is associated with increased colorectal cancer incidence, possibly partially independent of BMI.     

Active and passive smoking and breast cancer risk in middle-aged Japanese women

To examine the hypothesis that tobacco smoke is associated with the risk of female breast cancer, we estimated the relative risks of active and passive smoke in middle-aged Japanese women in a population-based prospective study. The cohort consisted of residents in 4 public health center areas, aged 40 to 59 years. A self-administered questionnaire survey was conducted in 1990. This analysis included 21,805 subjects, 180 of whom had developed breast cancer by December 31, 1999. When the reference was defined as never-active smokers without passive smoking, adjusted relative risks (RRs) were 1.9 (95% confidence interval [CI] = 1.0-3.6) in current active smokers, 1.2 (95% CI = 0.4-4.0) in ex-active smokers and 1.2 (95% CI = 0.8-1.6) in never-active smokers with passive smoking. The elevated risk for ever-smokers was clearly observed in premenopausal women at baseline (RR = 3.9, 95% CI = 1.5-9.9) but not in postmenopausal women (RR = 1.1, 95% CI = 0.5-2.5). In never-active smokers, the adjusted RR for passive smoking, residential or occupational/public tobacco smoke exposure was 1.1 (95% CI = 0.8-1.6). In premenopausal women, passive smoking increased the risk (RR = 2.6; 95% CI = 1.3-5.2) but not in postmenopausal women (RR = 0.7; 95% CI = 0.4-1.0). We conclude that tobacco smoking increases the risk of female breast cancer in premenopausal women.     

Relation of body mass index to cancer risk in 362,552 Swedish men

Background Obesity has been linked with increased risk for cancers of the colon, kidney, breast, endometrium and gallbladder. For other cancer sites, the relationship with obesity is less well quantified, and the effect of weight change on cancer risk is unclear. Methods We examined the health records of 362,552 Swedish men who underwent at least one physical examination from 1971 to 1992, and were followed until death or the end of 1999. Incident cancer cases were identified by linkage to the Swedish cancer registry. Poisson regression models were used to estimate relative risks of cancer for both body-mass index (BMI) at baseline exam and, in a subgroup of 107,815 men, change in BMI after six years of follow-up, adjusting for age and smoking status. Results Compared to men of normal weight, obese men had a significantly increased risk of all cancers combined (RR = 1.1; 95% CI = 1.0–1.2). The risks were most pronounced for esophageal adenocarcinoma (RR = 2.7; 95% CI = 1.3–5.6), renal cell carcinoma (RR = 1.8; 95% CI = 1.4–2.4), malignant melanoma (RR = 1.4; 95% CI = 1.1–1.7), and cancers of the colon (RR = 1.7; 95% CI = 1.5–2.0), rectum (RR = 1.4; 95% CI = 1.1–1.7), and liver (RR = 3.6; 95% CI = 2.6–5.0). Risk of esophageal squamous cell carcinoma was elevated for underweight men whose BMI was less than 18.5 (RR = 3.1; 95% CI = 1.1–8.3). An excess risk for cancers of the pancreas and connective tissue was observed only among nonsmokers. Compared to men whose weight remained stable, men with more than a 15% increase in BMI after six years of follow-up had an elevated risk of pancreas and renal cell cancers. Conclusions Obesity and weight gain increase the risk for several forms of cancer in men, and underscore the need for further study into carcinogenic mechanisms and preventive interventions.     

Dietary fiber and colorectal cancer risk: the multiethnic cohort study

OBJECTIVE: To investigate the association of dietary fiber with colorectal cancer METHODS: A total of 85,903 men and 105,108 women completed a quantitative food frequency questionnaire in 1993-1996. A total of 1,138 men and 972 women were subsequently diagnosed with adenocarcinoma of the large bowel. Cox proportional hazards models were used to calculate multivariate adjusted relative risks (RR) and 95% confidence intervals (95% CI) for colorectal cancer. RESULTS: High consumers of dietary fiber were more active, less overweight, and less likely to be cigarette smokers than low consumers in both sexes. Fiber was inversely associated with colorectal cancer risk after adjustment for age and ethnicity in men (RR = 0.49; 95% CI, 0.41-0.60, highest vs. lowest quintile) and women (RR = 0.75; 95% CI, 0.61-0.92). After further adjustment for lifestyle and dietary factors, the inverse association remained significant in men (RR = 0.62; 95% CI, 0.48-0.79), but not in women (RR = 0.88; 95% CI, 0.67-1.14). Adjustment for the combination of replacement hormone use with either cigarette smoking or body mass index accounted for the lack of association with fiber in women. CONCLUSION: Dietary fiber was inversely associated with colorectal cancer risk in men, but its relation to replacement hormone use and other factors affected its inverse association in women.     

Alcohol consumption, smoking, and subsequent risk of colorectal cancer in middle-aged and elderly Japanese men and women: Japan Public Health Center-based prospective study.

Few studies have examined the association of alcohol consumption and cigarette smoking with colorectal cancer in Asian populations whose genetic susceptibility to these factors are different from Western populations. We investigated this association and the joint effect of these factors, and estimated the population-attributable fraction to clarify the public health impact on a Japanese population, based on a prospective study. We analyzed the 10-year (cohort I) and 7-year (cohort II) follow-up data of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease, derived from 90,004 (42,540 male and 47,464 female) middle-aged and elderly Japanese. We identified 716 (457 in men and 259 in women) newly diagnosed cases of colorectal cancer. Both alcohol consumption and smoking were clearly associated with colorectal cancer in men, after adjusting for age, family history of colorectal cancer, body mass index, and physical exercise. Regular heavy drinking of 150 g/week or more of ethanol showed a statistically significant increased risk compared with nondrinkers: relative risks (RRs) were 1.4 [95% confidence interval (CI), 1.1-1.9] for 150-299 g/week and 2.1 (95% CI, 1.6-2.7) for 300 g/week or more. On the contrary, regular ethanol consumption was not associated with colorectal cancer (RR, 0.7; 95% CI, 0.4-1.1) in women. In terms of smoking, the RRs were 1.4 (95% CI, 1.1-1.8) for current smokers and 1.3 (95% CI, 0.98-1.7) for ex-smokers compared with never-smokers in men. The risk of smoking in women was similar to that in men, although not statistically significant. The colorectal cancer risk with 300 g/week or more of ethanol in current smokers was estimated at 3.0 (95% CI, 1.8-5.1) compared with nondrinkers among nonsmokers in men. Colorectal cancer attributable to alcohol consumption or smoking was estimated to be 46%. In conclusion, approximately half of the colorectal cancer cases may be preventable by tobacco and alcohol controls in middle-aged and elderly Japanese men.     

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.     

Socio-economic and lifestyle factors associated with the risk of prostate cancer

International and interethnic differences in prostate cancer incidence suggest an environmental aetiology, and lifestyle and socio-economic factors have been studied, but with divergent results. Information on a cohort of 22,895 Norwegian men aged 40 years and more was obtained from a health examination and two self-administered questionnaires. Information on incident cases of prostate cancer was made available from the Cancer Registry. We used the Cox proportional hazards model to calculate incidence rate ratios as estimates of the relative risk (RR) with 95% confidence interval (CI). Reported P-values are two-sided. During a mean follow-up of 9.3 years, 644 cases were diagnosed. Risk was elevated among men in occupations of high compared to low socio-economic status (RR = 1.30; 95% CI 1.05-1.61), and among men with high education compared to the least educated (RR = 1.56; 95% CI 1.11-2.19). A RR of 1.56 (95% CI 0.97-2.44) suggests a higher risk among divorced or separated men, compared with married men. We also found indications of a weak negative association with leisure-time physical activity (RR = 0.80; 95% CI 0.62-1.03 for high vs low activity), a weak positive association with increasing number of cigarettes (P = 0.046), while alcohol consumption was not related to the risk of prostate cancer. These results show that high socio-economic status is associated with increased risk of prostate cancer, and that divorced or separated men might be at higher risk than married men. Data from this study also indicate that high levels of physical activity may reduce prostate cancer risk.     

Association between atherosclerosis and female lung cancer--a Danish cohort study

Patients suffering from atherosclerotic diseases are prone to repeated episodes of ischemia/reperfusion that has been demonstrated to induce oxidative stress by formation of oxygen free radicals. It might therefore be expected that such endogenously exposure to free radicals increases the individual cancer risk in patients with atherosclerotic diseases. We therefore studied the sex-specific risk of lung cancer and other cancers in atherosclerotic patients in a prospective study conducted in the Copenhagen area. The study cohort was linked to the Danish Hospital Discharge Register and we identified 2261 1-year survivors of atherosclerotic diseases through 1977 and 1993, while 26150 of the study subjects had no record of an atherosclerotic diagnosis. After linkage to the Danish Cancer Registry associations between atherosclerosis and cancer were analysed for each sex separately by means of Cox proportional hazard regression models. Atherosclerotic women had a significant RR of lung cancer of 3.26 (95% CI: 1.95-5.46) compared to non-atherosclerotic women after adjustment for age, calendar period, study population, smoking habits, school education and alcohol consumption. No significant risk of male lung cancer, RR=1.12 (95% CI: 0.77-1.64), or other smoking-related cancers in either sex was observed after multivariate adjustment. Atherosclerosis did not predict non-smoking-related cancers in general in either men, RR=0.91 (95% CI 0.69-1.20), or women, RR=0.93 (95% CI: 0.64-1.35). We hypothesize that oxidative stress due to episodes of ischemia/reperfusion increases the risk of lung cancer in atherosclerotic females because of a gender specific susceptibility to oxidative DNA damage.