Evaluation based on systematic review of epidemiological evidence among Japanese populations: tobacco smoking and total cancer risk

BACKGROUND: We evaluated the association between tobacco smoking and total cancer risk among Japanese populations based on a systematic review of epidemiological evidence. METHODS: Original data were obtained from searches of MEDLINE using PubMed, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain summary estimates of association. RESULTS: A total of eight cohort studies were identified. In men, all studies consistently showed a moderately increased risk of total cancer in current smokers compared with never-smokers. In women, an increase in risk was seen but was weaker than in men. The summary relative risk was estimated as 1.53 (95% confidence interval 1.41-1.65). CONCLUSION: We conclude that there is convincing evidence that current tobacco smoking moderately increases the risk ( approximately 1.5 times) of total cancer in the Japanese population compared with never-smoking Japanese.     

Tobacco smoking and lung cancer risk: an evaluation based on a systematic review of epidemiological evidence among the Japanese population

BACKGROUND: Although tobacco smoking is the best established risk factor for lung cancer, the association is not as strong among Japanese as among Western populations. It would be of value, therefore, to quantify that association in Japan based on a systematic review of epidemiological evidence for the primary prevention of lung cancer. METHODS: Original data were obtained from MEDLINE searches using PubMed, supplemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of the association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was also conducted to estimate the summary measure of those associations. RESULTS: A total of 8 cohort studies and 14 case-control studies were identified, almost all of which consistently showed a strong association of current smoking with the risk of lung cancer. The summary relative risk for current smokers versus never smokers was estimated as 4.39 (95% confidence interval 3.92-4.92) for men and 2.79 (95% confidence interval 2.44-3.20) for women. Cohort studies and case-control studies gave reasonably consistent summary measures. The summary relative risks were 11.7 and 2.30 for squamous cell carcinoma and adenocarcinoma, respectively, in men, and were 11.3 and 1.37 correspondingly in women. CONCLUSION: There is convincing evidence that tobacco smoking strongly increases the risk of lung cancer in the Japanese population, with the relative risk for current smokers compared with never smokers measuring around 4.4 for men and 2.8 for women.     

Tobacco smoking and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: It is unclear whether tobacco smoking is related to colorectal cancer risk in Japan. We evaluated the association among the Japanese population based on a systematic review of epidemiologic evidence. METHODS: Original data were obtained from searches of MEDLINE using PubMed, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: A total of six cohort studies and 15 case-control studies were thus identified. A substantial degree of heterogeneity was observed in the association between smoking and colon cancer; most case-control studies published before 1994 reported an inverse association, whereas studies conducted over the last decade did not find any significant association. Recent cohort studies have shown a non-significant 20-40% increase in colon cancer risk associated with current smoking. Several recent case-control studies and some cohort studies have identified a weak to strong positive association between smoking and rectal cancer. CONCLUSION: We conclude that tobacco smoking possibly increases the risk of colorectal cancer among the Japanese population. More specifically, tobacco smoking may possibly increase the risk of rectal cancer; however, epidemiologic evidence is still insufficient to demonstrate any clear association with colon cancer.     

Alcohol drinking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

Background: We reviewed epidemiologic studies on the association betweenalcohol drinking and gastric cancer among the Japanese population.This report is one of a series of articles by our research group,which is evaluating the existing evidence concerning the associationbetween health-related lifestyles and cancer. Methods: Original data were collected by searches of MEDLINE using PubMed,or searches of the Ichushi database, complemented with manualsearches. Evaluation of associations was based on the strengthof evidence and the magnitude of association, together withbiological plausibility as evaluated previously by the InternationalAgency for Research on Cancer. Results: Of the 11 cohort studies evaluated, nine showed no associationbetween alcohol drinking and gastric cancer, and one study showeda strong positive association among men. All of 11 case–controlstudies found no association between alcohol drinking and gastriccancer. By anatomical subsites of gastric cancer, only threestudies have evaluated the association between alcohol drinkingand gastric cancer, and one cohort study found a positive associationfor cardia and upper-third gastric cancer in men. Few studiesconducted among the Japanese population have made a detailedassessment of alcohol drinking, possible important confoundingfactors such as smoking and diet and anatomical subsites ofgastric cancer. Conclusion: We conclude that epidemiologic evidence for an association betweenalcohol drinking and gastric cancer risk remains insufficientdue to the methodological quality of studies that have beenconducted among the Japanese population.     

Alcohol drinking and total cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: We conducted a systematic review of epidemiological evidence to evaluate the association between alcohol drinking and total cancer risk among the Japanese population. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. RESULTS: Of eight cohort studies identified, six studies, three of which included women, were subjected to evaluation. In men, all six studies showed a weak to moderate positive association between alcohol drinking and total cancer risk. While light drinking had little effect on total cancer risk, heavy drinking of more than 46-69 g of alcohol per day contributed to total cancer risk for most of these Japanese populations. However, no association was reported in women in any of the three studies. CONCLUSION: We conclude that there is convincing evidence that alcohol drinking increases the risk of total cancer in the Japanese population, specifically among heavy drinking men.     

Tobacco smoking and breast cancer risk: an evaluation based on a systematic review of epidemiological evidence among the Japanese population

BACKGROUND: Our research group undertook an appraisal of the body of epidemiological studies on cancer in Japan to evaluate the existing evidence concerning the association between health-related lifestyles and cancer. As tobacco smoking may be one of the few modifiable risk factors for breast cancer, we focused on the association between tobacco smoking and the risk of breast cancer in this review. METHODS: A MEDLINE search was conducted to identify epidemiological studies on the association between smoking and breast cancer incidence or mortality among the Japanese from 1966 to 2005. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: Three cohort studies and eight case-control studies were identified. The relative risk (RR) or odds ratio (OR) of breast cancer for current smokers ranged from 0.71 to 6.26 in these studies. A significantly increased risk among current smokers compared with never smokers (RR = 1.7) was reported in one out of the three cohort studies. Moderate or strong associations between smoking and breast cancer risk (OR > 2.0) were observed in four of the eight case-control studies. Experimental studies have supported the biological plausibility of a positive association between tobacco smoking and breast cancer risk. CONCLUSION: We conclude that tobacco smoking possibly increases the risk of breast cancer in the Japanese population.     

Alcohol drinking and lung cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: The relationship between alcohol consumption and risk of lung cancer is controversial. Based on a systematic review of epidemiologic evidence, we evaluated this association among the Japanese population, who may be more susceptible to alcohol-related diseases than Western populations. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: We identified seven cohort studies and two case-control studies. One cohort study demonstrated a strong positive association between alcohol drinking and the risk of female lung cancer, but the association almost disappeared after adjustment for smoking. The other eight studies showed a weak positive or no association. Although smoking is the best-established risk factor for lung cancer, only five cohort studies presented smoking-adjusted risks out of all nine identified. Furthermore, only two studies explicitly reported the risk estimate for ex-drinkers who may have quit alcohol drinking after the development or diagnosis of the disease and have an apparently higher risk. CONCLUSION: We conclude that the epidemiologic evidence on the association between alcohol drinking and lung cancer risk remains insufficient in terms of both the number and methodological quality of studies among the Japanese population.     

Alcohol drinking and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: We reviewed epidemiological studies on alcohol drinking and breast cancer among the Japanese population. This report is one among a series of articles by our research group evaluating the existing evidence concerning the association between health-related lifestyles and cancer. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: Three cohort studies and eight case-control studies were identified. There were inconsistent results regarding alcohol drinking and breast cancer risk among cohort studies. A significant positive association was observed in one, but another showed nonsignificant inverse association. Out of the eight case-control studies, two studies showed a significantly increased risk among women who drink daily and who had higher intake of alcohol, respectively. Experimental studies have supported the biological plausibility of a positive association between alcohol drinking and breast cancer risk. CONCLUSION: We conclude that epidemiologic evidence on the association between alcohol drinking and breast cancer risk remains insufficient in terms of both the number and methodological quality of studies among the Japanese population.     

Cigarette smoking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among Japanese

BACKGROUND: Emerging epidemiologic data suggest that cigarette smoking may increase the risk of primary liver cancer. We evaluated this association based on a systematic review of epidemiologic evidence among Japanese populations. METHODS: Original data were obtained from MEDLINE searches using PubMed, complemented with manual searches. The evaluation was performed in terms of the magnitude of association ('strong', 'moderate', 'weak' or 'no association') in each study and the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient'), together with biological plausibility as previously done by the International Agency for Research on Cancer. RESULTS: A total of 12 cohort studies and 11 case-control studies were identified. Nine cohort studies (two with adjustment for hepatitis B and C virus infections and seven without it) reported weak to strong positive associations between smoking and liver cancer, with dose-response relationships shown in three studies. Five case-controls studies (three with the virus adjustment and two without it) demonstrated such positive associations, with a dose-response relationship shown in only one study, while in six case-control studies, the observed associations were judged to be of the lowest magnitude or inverse due to the lack of any dose-response relationship. CONCLUSION: We conclude that cigarette smoking 'probably' increases the risk of primary liver cancer among the Japanese. Potential confounding by hepatitis virus infection and virus-smoking interactions need to be addressed in future studies.     

Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.     

Alcohol drinking and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: It remains unclear whether alcohol drinking is causally associated with colorectal cancer. On the basis of a systematic review of epidemiological evidence, we evaluated this association among the Japanese population, who may be more susceptible to alcohol-related diseases than Western populations. METHODS: Original data were obtained from searches of MEDLINE using PubMed, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: We identified 5 cohort studies and 13 case-control studies. A moderate or strong positive association was observed between alcohol drinking and colon cancer risk in all large-scale cohort studies, with some showing a dose-response relation, and among several case-control studies. The risk of colon or colorectal cancer was increased even among moderate drinkers consuming <46 g of alcohol per day, levels at which no material increase in the risk was observed in a pooled analysis of Western studies. A positive association with rectal cancer was also reported, but it was less consistent, and the magnitude of the association was generally weaker compared with colon cancer. CONCLUSION: We conclude that alcohol drinking probably increases the risk of colorectal cancer among the Japanese population. More specifically, the association for the colon is probable, whereas that for the rectum is possible.     

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.     

TP53 mutation spectrum in lung cancer is not different in women and men.

Whether women are more susceptible to lung cancer than men has been controversial. Several case-control studies suggested that women have greater risk of lung cancer compared with men at similar levels of cigarette smoking, whereas some large cohort studies failed to observe this association. Other studies indicated that lung cancer may have biological characteristics and mechanisms of carcinogenesis that are gender specific. Therefore, we hypothesized that women are more susceptible to the carcinogenic effects of tobacco smoke exposure, as evidenced by a higher frequency of G:C-to-T:A somatic mutations in tumors from women in comparison with men at similar levels of tobacco smoke exposure. To investigate our hypothesis, we examined the TP53 mutational spectrum in a case-only (102 women and 201 men) series study where complete smoking information was available. A similar frequency and type of somatic TP53 mutations were observed in women and men. In conclusion, our study indicates that the TP53 mutation spectrum is similar in women and men. Our results are consistent with a recent large cohort study and summary of previous cohort studies, suggesting that women likely have equivalent susceptibility to lung cancer as men.     

Passive smoking exposure and female breast cancer mortality

BACKGROUND: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women. METHODS: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure. RESULTS: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8-1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1. 2; 95% CI = 0.8-1.8). CONCLUSIONS: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy.     

Women's susceptibility to tobacco carcinogens

STUDY OBJECTIVES: To assess lung cancer risk of smoking women relative to that of equally smoking men. METHODS: The study base was constituted by baseline CT screenings for lung cancer on 1202 women and 1288 men, at least 40 years of age and with at least 10 pack-years of cigarette smoking. The prevalence-odds (incidence-density) ratio contrasting women with men was calculated. Confoundings by age and the particulars of smoking history were controlled in logistic regression analysis. RESULTS: For the prevalence-odds ratio contrasting women with men, upon control of age and smoking history, the point estimate was 2.7 and the 95% interval estimate 1.6-4.7. The diagnosed cancers were of equally 'aggressive' types between the two genders. CONCLUSIONS: At variance with evidence from cohort studies, this evidence from a screening experience calls for further consideration of the hypothesis that women are more susceptible to tobacco carcinogens than are men.     

Smoking and Cancer Risk in Korean Men and Women

OBJECTIVE: In Korea, male smoking prevalence is among the world's highest, and mortality rates from smoking-caused cancers, particularly lung cancer, are escalating. This cohort study examined the effects of cigarette smoking on the risk of cancer mortality and incidence, and characterized the relationship of cancer risk with the amount and duration of cigarette smoking. METHOD: A nine-year prospective cohort study was carried out on 1,212,906 Koreans, 30-95 years of age. The study population includes participants in a national insurance program, who completed a questionnaire on smoking and other risk factors. The main outcome measures were death from cancer and cancer incidence, obtained through record linkage. At baseline, 472,970 men (57.0%) and 20,548 (5.4%) women were current cigarette smokers. RESULTS: In multivariate Cox proportional hazards models, controlling for age, current smoking among men increased the risks of mortality for cancer of the lung (relative risk (RR), 4.6; 95% confidence interval (CI), 4.0-5.3) and other cancers, including larynx, bile duct, esophagus, liver, stomach, pancreas, bladder, and also leukemia. Current smoking among women increased the risk of lung cancer mortality (RR = 2.5, 95% CI = 2.0-3.1). Similar results were found for incidence among men and women. CONCLUSION: In Korea, smoking is an independent risk factor for a number of major cancers. The findings affirm the need for aggressive tobacco control in Korea in order to minimize the epidemic of smoking-caused disease.     

Risk factors for breast cancer: epidemiological evidence from Japanese studies

Although our understanding of the etiology of breast cancer has improved, many well-known risk factors are not modifiable and present knowledge has proved insufficient to allow the disease to be overcome. Indeed, incidence and mortality among Japanese women have increased over the past three decades. Here, we review epidemiological evidence from our cohort and case-control studies among Japanese women in comparison with other published findings. Our studies confirm the important role of established factors derived primarily from Western populations, such as menstrual and reproductive factors, anthropometric factors, physical activity, and alcohol intake, in the development of breast cancer. In addition, we provide further evidence to better understand the role of traditional Japanese foods in the etiology of breast cancer. Our cohort study found that a higher intake of isoflavone and higher levels of plasma genistein, but not daidzein, were associated with a decreased risk of breast cancer. Our case-control studies reveal a dose-response pattern for these compounds; specifically, decreased risk as women move from "no" to "moderate" intake and leveling off thereafter. In addition, gene-environment interactions have been revealed in the effects of isoflavones. The evidence reviewed suggests that isoflavone has a protective effect against breast cancer in Asian populations. Conversely, our cohort study did not observe an inverse association between breast cancer risk and the intake of green tea and/or the plasma level of tea polyphenols, but we did find an association between increased risk and active and passive smoking. In conclusion, based on current knowledge, primary prevention according to individual lifestyle modification should focus on alcohol intake, weight control, physical activity, and tobacco smoking.     

Passive smoking and lung cancer in Japanese non-smoking women: a prospective study

Although smoking is a major cause of lung cancer, the proportion of lung cancer cases among Japanese women who never smoked is high. As the prevalence of smoking in Japan is relatively high in men but low in women, the development of lung cancer in non-smoking Japanese women may be significantly impacted by passive smoking. We conducted a population-based prospective study established in 1990 for Cohort I and in 1993 for Cohort II. The study population was defined as all residents aged 40-69 years at the baseline survey. 28,414 lifelong non-smoking women provided baseline information on exposure to tobacco smoke from their husband, at the workplace and during childhood. Over 13 years of follow-up, 109 women were newly diagnosed with lung cancer, of whom 82 developed adenocarcinoma. Compared with women married to never smokers, hazard ratio (HR) [95% confidence interval (CI)] for all lung cancer incidence in women who lived with a smoking husband was 1.34 (95% CI 0.81-2.21). An association was clearly identified for adenocarcinoma (HR 2.03, 95% CI 1.07-3.86), for which dose-response relationships were seen for both the intensity (p for trend = 0.02) and amount (p for trend = 0.03) of the husband's smoking. Passive smoking at the workplace also increased the risk of lung cancer (HR 1.32, 95% CI 0.85-2.04). Moreover, a higher risk of adenocarcinoma was seen for combined husband and workplace exposure (HR 1.93, 95% CI 0.88-4.23). These findings confirm that passive smoking is a risk factor for lung cancer, especially for adenocarcinoma among Japanese women.     

Meat consumption and colorectal cancer risk in Japan: The Takayama study

Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population‐based prospective cohort study in Japan. Participants were 13 957 men and 16 374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population‐based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest versus lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03, 1.79) for total meat (P for trend = 0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (P for trend = 0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.     

Smoking and colorectal cancer: different effects by type of cigarettes?

Although smoking is suggested to be a risk factor for colorectal cancer, the evidence to date is conflicting and may be confounded. Moreover, the effect of tobacco smoke may vary by time since initiation, type of tobacco product, anatomic subsites, and among ethnic groups. Data were derived from two consecutive population-based case-control studies conducted among Caucasians, Japanese, Native Hawaiians, Filipinos, and Chinese in Hawaii, including 1,959 ethnicity-, sex-, and age-matched case-control pairs. A lifetime history of smoking for different tobacco products and information on other risk factors were obtained by in-person interviews. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated using conditional logistic regression models with adjustment for potential confounders. Subjects who ever smoked were at an increased risk of colorectal cancer compared with never smokers (OR, 1.23; 95% CI, 0.99-1.52 for men and OR, 1.27; 95% CI, 1.01-1.59 for women). Increasing quartiles of pack-years over all tobacco products showed a clear dose-dependent association in men [for the highest quartile, Q4 (>40 pack-years) versus never smokers: OR, 1.48; 95% CI, 1.12-1.96; P(trend) = 0.002]. The dose-response trend was also present in women [for the highest quartile, Q4 (>30 pack-years) versus never smokers: OR, 1.38; 95% CI, 0.91-1.95; P(trend) = 0.04] and each ethnic group. There was a suggestion of a difference in risk with type of tobacco product. Non-filtered cigarettes increased risk of both colon and rectal cancer [for Q4 versus never smokers: OR, 1.59; 95% CI, 1.15-2.21; P(trend) = 0.001 and OR, 1.84; 95% CI, 1.18-2.86; P(trend) = 0.02, respectively], whereas filtered cigarettes seemed to increase risk of rectal but not colon cancer (OR, 1.37; 95% CI, 0.88-2.13; P(trend) = 0.06 and OR, 1.05; 95% CI, 0.79-1.39; P(trend) = 0.98, respectively). The effect of smoking was not limited to the distant past, and accumulated pack-years of smoking seemed to be more important than the time in which smoking occurred. The data from this large study corroborate previous reports of a positive association between smoking and colorectal cancer and suggest that the association may vary by type of cigarette.