Increased risk of colorectal cancer among smokers: Results of a 26-year follow-up of us veterans and a review

To clarify the relationship between tobacco use and risk of colorectal cancer, we evaluated a cohort of 248,046 American veterans followed prospectively for 26 years. In comparison with veterans who had never used tobacco, the risk of death was significantly increased for colon cancer and rectal cancer among current and former cigarette smokers and among pipe or cigar smokers, controlling for social class and occupational physical activity. Rectal-cancer risk was also significantly elevated among users of chewing tobacco or snuff. For both sites, risk increased significantly with pack-years, earlier age at first use, and number of cigarettes. These results reinforce 2 recent reports of the association of cigarette smoking and colorectal cancer in men and women. Inconsistencies in the findings of earlier epidemiologic studies appear to be due in large part to differences in length of follow-up or in choice of controls. Studies with at least 20 years of follow-up or population-based controls have tended to find elevated risk with tobacco smoking, while those with shorter follow-up or hospital controls have not. This, plus the strength and consistency of the association of smoking and colon polyps, suggest that smoking may primarily affect an early stage in the development of colon cancer. If this association is causal, tobacco use may be responsible for 16% of colon-cancer and 22% of rectal-cancer deaths among these veterans.     

Lower lung cancer rates in Jewish smokers in Israel and the USA

Lung cancer rates in Israeli Jews have remained stable over the last five decades and are much lower than in most developed countries despite high historical smoking rates. We compared lung cancer risk in Jews and non‐Jews in Israel and in the United States. Data were derived from a population‐based, case–control study in Israel (638 cases, 496 controls) to estimate lung cancer risk associated with smoking. Data were also acquired from a case–control study in the United States with information on religious affiliation (5,093 cases, 4,735 controls). Smoking was associated with lung cancer risk in all religion/gender groups in both studies. However, major differences in risk magnitude were noted between Jews and non‐Jews; ever smoking was associated with a moderately elevated risk of lung cancer in Jewish men and women in Israel (OR = 4.61, 2.90–7.31 and OR = 2.10, 1.36–3.24, respectively), and in Jewish men and women in the United States (OR = 7.63, 5.34–10.90 and OR = 8.50, 5.94–12.17) but were significantly higher in Israeli non‐Jewish men (OR = 12.96, 4.83–34.76) and US non‐Jewish men and women (OR = 11.33, 9.09–14.12 and OR = 12.78, 10.45–15.63). A significant interaction between smoking and religion was evident in light, moderate and heavy male and female smokers. The differences in risk level between Israeli Jews and non‐Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions). Data from the two studies support the notion of a reduced risk of lung cancer in Jewish compared to non‐Jewish smokers in different areas of the world.     

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.     

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.     

International renal-cell cancer study. I. Tobacco use

The relationship between renal-cell cancer (RCC) and tobacco use was investigated in an international, multicenter, population-based case-control stud/. Coordinated studies were conducted in Australia, Denmark, Germany, Sweden and the United States using a shared protocol and questionnaire. A total of 1,732 cases (1,050 men, 682 women) and 2,309 controls (1,429 men, 880 women) were interviewed for the study. No association was observed between risk and use of cigars, pipes or smokeless tobacco. A statistically significant association was observed for cigarette smoking, with current smokers having a 40% increase in risk [relative risk (RR) = 1.4, 95% confidence interval (CI) 1.2–1.7]. Risk increased with intensity (number of cigarettes) and duration (years smoked). Among current smokers the RR for pack-years rose from I.I (95% CI 0.8–1.5) for <15.9 pack years to 2.0 (95% CI 1.6–2.7) for >42 pack years (p for trend < 0.001). Long-term quitters (> 15 years) experienced a reduction in risk of about 15–25% relative to current smokers. Those who started smoking late (>24 years of age) had about two-thirds the risk of those who started young (< 12 years of age). Overall, the findings of this pooled analysis confirm that cigarette smoking is a causal factor in the etiology of RCC. © 1995 Wiley-Liss, Inc.     

Cigarette smoking and colorectal cancer mortality in the cancer prevention study II

BACKGROUND: Recent studies suggest that long-term cigarette smoking is associated with an increased risk of colorectal cancer. Whether the association is causal or due to confounding remains unclear. METHODS: We examined cigarette smoking in relation to colorectal cancer mortality, evaluating smoking duration and recency and controlling for potential confounders in the Cancer Prevention Study II. This prospective nationwide mortality study of 1 184 657 adults (age > or =30 years) was begun by the American Cancer Society in 1982. After exclusions, our analytic cohort included 312 332 men and 469 019 women, among whom 4432 colon or rectal cancer deaths occurred between 1982 and 1996 among individuals who were cancer free in 1982. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, were intermediate among former smokers, and were lowest in lifelong nonsmokers. The multivariate-adjusted RR (95% CI) for current compared with never smokers was 1.32 (1.16-1.49) among men and 1.41 (1.26-1.58) among women. Increased risk was evident after 20 or more years of smoking for men and women combined as compared with never smokers. Risk among current and former smokers increased with duration of smoking and average number of cigarettes smoked per day; risk in former smokers decreased significantly with years since quitting. If the multivariate-adjusted RR estimates in this study do, in fact, reflect causality, then approximately 12% of colorectal cancer deaths among both men and women in the general U.S. population in 1997 were attributable to smoking. CONCLUSIONS: Long-term cigarette smoking is associated with increased risk of colorectal cancer mortality in both men and women. Clear reduction in risk is observed with early smoking cessation.     

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.     

Smoking,snus use and risk of right‐ and left‐sided colon,rectal and anal cancer: A 37‐year follow‐up study

Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included 336,381 male Swedish construction workers with detailed information on tobacco use at cohort entry in 1971–1992. Complete follow‐up through 2007 was accomplished by means of linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards regression models estimated relative risks, adjusted for age and body mass index. Subjects who were never‐users of any tobacco served as reference. After up to 37 years of follow‐up, pure smoking was associated with a marginally increased risk of colon cancer (HR 1.08, 95% CI 0.99–1.19), a modestly elevated risk of rectal cancer (HR 1.16, 95% CI 1.04–1.30) and a substantial excess risk of anal cancer (HR 2.41, 95% CI 1.06–5.48). Snus use was not significantly associated with an increased risk of colorectal or anal cancer, although the point estimate for colon cancer was similar to that observed among smokers. Swedish data provide meager support for the association between tobacco use and colorectal cancer. A general tendency among Swedish men to quit smoking in recent decades might have attenuated true associations. A link between smoking and anal cancer was confirmed.     

Cigarette smoking and the risk of colorectal cancer among men: a prospective study in Japan.

The association between cigarette smoking and the risk of colorectal cancer remains controversial. We examined this association using a population-based prospective cohort study in Miyagi, Japan. In 1990, we delivered a self-administered questionnaire on cigarette smoking and other health habits to 25 279 men who were 40-64 years of age and lived in 14 municipalities of Miyagi Prefecture. A total of 22 836 men responded (90.3% response rate). During 7 years of follow-up (158 376 person-years), we identified 188 patients of colorectal cancer. Relative risks and 95% confidence intervals were estimated by the Cox proportional-hazards regression analysis with adjustment for potential confounders. The multivariate-adjusted relative risks (95% confidence interval) of colorectal cancer for past smokers and current smokers compared with those who had never smoked were 1.73 (1.04-2.87) and 1.47 (0.93-2.34), respectively. Among current smokers, both a higher number of cigarettes smoked per day and an earlier age at which smoking had started were associated with a significant linear increase in risk (P for trend <0.05). Our findings are consistent with the hypothesis that cigarette smoking is associated with a higher risk of colorectal cancer in men.     

Gender and lung cancer.

Although lung cancer is the leading cause of cancer death among men and women in the United States, female smokers appear to be at increased risk. After controlling for the number of cigarettes smoked, female sex imparts a significant, independent risk for most histologic types of lung cancer. Cigarette smoking, genetics, and endocrine factors may interact to contribute to the disparity in lung cancer risk between the sexes. Estrogens have direct and indirect actions in the lung, and estrogen has been implicated in lung carcinogenesis in female smokers. This review of the literature will focus on endocrine factors and tobacco carcinogens as risk factors for lung cancer in women.     

Smoking-attributable cancer mortality in 1991: is lung cancer now the leading cause of death among smokers in the United States?

Findings from the new American Cancer Society prospective study of 1.2 million men and women indicate that mortality risks among smokers have increased substantially for most of the eight major cancer sites causally associated with cigarette smoking. Lung cancer risk for male smokers doubled, while the risk for females increased more than fourfold. On the basis of the new American Cancer Society relative risks, we project that cigarette smoking alone will contribute to slightly more than 157,000 of the 514,000 total cancer deaths expected to occur in the United States in 1991. Overall, smoking directly contributes to 21.5% of all cancer deaths in women but 45% of all cancer deaths in men. It would also appear that lung cancer has now displaced coronary heart disease as the single leading cause of excess mortality among smokers in the United States.     

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.     

The role of tobacco in cancer health disparities

Although public health efforts have dramatically reduced the prevalence of smoking in the past several decades, smoking remains the leading cause of preventable morbidity and mortality in the United States. Moreover, tobacco use is becoming increasingly concentrated among individuals with the lowest levels of education, income, and occupational status. Profound racial/ethnic and socioeconomic status (SES) disparities exist for tobacco-related cancer incidence and mortality, and for access to and quality of cancer treatment. Furthermore, racial/ethnic minority and low SES smokers have greater difficulty quitting smoking, are less likely to use effective resources for quitting, and have limited access to evidence-based cessation treatments. Widespread implementation of population-based tobacco cessation approaches may have had the unintended effect of increasing tobacco-related cancer health disparities. It is crucial that vulnerable populations of smokers be provided with effective and accessible treatments for tobacco dependence, as this would have a profound impact on reducing tobacco-related cancer health disparities.     

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.     

Cigarette smoking and risk of prostate cancer among Singapore Chinese

Prospective epidemiologic studies conducted in Western populations support an association between current smoking and aggressive subtypes of prostate cancer. In Singapore, where prostate-specific antigen is not used for population-wide screening, prostate cancer incidence has tripled within the past two decades. Using Cox regression methods, we examined the relationship between smoking and prostate cancer established between 1993 and 1998 in a cohort of 27,293 Singapore Chinese men. As of December 2006, 250 incident prostate cancer cases were diagnosed. In our cohort, 42.2% reported never smoking cigarettes, 15.7% quit over 5 years ago (long-term former), 5.7% quit within the past 5 years (recent former), and 36.4% were current smokers. From multivariable models, we observed no association with smoking status, age at starting to smoke, years smoked, or number of cigarettes per day. Among recent former and current smokers combined, we observed a small positive association for earlier age at starting to smoke that was somewhat stronger for nonadvanced disease (hazard ratio = 1.63, 95% confidence interval: 0.85, 3.12, for <15 years versus nonsmokers). Smoking was not a major risk factor for prostate cancer in our Singapore Chinese cohort, a traditionally low risk population with parallel increases in incidence and mortality.     

Lung cancer in women

Lung cancer is one of the most important avoidable causes of death around the world, it is the most widespread carcinoma with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. At present more men than women die each year from lung cancer, but in recent years a rapid increase in lung cancer mortality has been observed among women in developed countries, contrasting with a levelling off or decrease among men. The rising trend in female lung cancer mortality has been observed to parallel with the past and current prevalence of cigarette smoking among women in the United States and elsewhere. An important role of other factors acting either as independent risk factors or interacting with the effect of smoking has been suggested by some studies among women, among them genetic, biologic and hormonal factors, and probably some factors related to the environment and lifestyle. There is a controversy concerning the claim that women have a different susceptibility to tobacco carcinogens, which might or might not be greater than men do. Since tobacco is far and away the strongest epidemiological risk factor for the development of lung cancer, comprehensive smoking control efforts are the priority in the prevention of lung cancer among women.     

Cigarette smoking and breast cancer risk: A long latency period?

The association between cigarette smoking and breast cancer risk remains unclear. Few studies have examined cigarette smoking of very long duration as there may not have been a sufficient number of long-term smokers in studies conducted before the 1980s. Therefore, we examined the association between smoking and breast cancer risk using data from participants in a randomized controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment and with up to 40 years of smoking duration at that time. Women with breast cancer diagnosed through 31 December 1993 were identified by linkage to the Canadian Cancer Database. Cox proportional hazards models were used to estimate rate ratios (RRs) and 95% confidence intervals (CIs). During an average of 10.6 years of follow-up, we observed 2,552 incident cases of breast cancer. We found a positive association between cigarette smoking and breast cancer risk, driven mainly by women who had smoked for several decades and who, therefore, had commenced smoking many years earlier. Relative to never-smokers, women who had smoked 40 years or more and 20 cigarettes/day or more were at the highest risk (RR = 1.83, 95% CI 1.29-2.61); for women who had commenced smoking 40 years or more before assessment (a measure of smoking latency rather than duration and intensity), the RR was 1.22 (95% CI 0.99-1.59). Our findings suggest that smoking of very long duration and high intensity may be associated with increased risk of breast cancer.     

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

BACKGROUND: We evaluated the association between tobacco smoking and gastric cancer risk among the Japanese population based on a systematic review of epidemiologic evidence. METHODS: Original data were collected by 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 evaluated previously by the International Agency for Research on Cancer. RESULTS: Ten cohort studies and 16 case-control studies were identified. In men, most studies reported moderate or strong positive associations between smoking and gastric cancer. In women, the positive association was weaker than in men. Of eight studies (three cohort studies and five case-case control studies), two cohort and three case control studies reported a weakly to strongly increased risk of gastric cancer. The summary relative risk for current smokers was estimated to be 1.56 (95% confidence intervals 1.36-1.80), 1.79 (1.51-2.12), 1.22 (1.07-1.38) for the total population, men and women, respectively. CONCLUSION: We conclude that there is convincing evidence that tobacco smoking moderately increases the risk of gastric cancer among the Japanese population.     

Glutathione S-transferase (GST) gene polymorphisms, cigarette smoking and colorectal cancer risk among Chinese in Singapore

Cigarette smoking is a risk factor for colorectal cancer. Putative colorectal procarcinogens in tobacco smoke include polycyclic aromatic hydrocarbons and heterocyclic aromatic amines that are known substrates of glutathione S-transferases (GSTs). This study examined the influence of functional GST gene polymorphisms on the smoking-colorectal cancer association in a population known to be minimally exposed to dietary sources of these procarcinogens. Incident cases of colorectal cancer (n = 480) and matched controls (n = 1167) were selected from the Singapore Chinese Health Study, a population-based prospective cohort of 63?257 men and women who have been followed since 1993. We determined the deletion polymorphisms of GSTM1 and GSTT1 and the functional polymorphism at codon 105 of GSTP1 for each subject. A three level composite GST index was used to examine if GST profile affected a smoker's risk of developing colorectal cancer. While there was no statistically significant association between cigarette smoking and colorectal cancer risk among subjects absent of any at-risk GST genotypes, smokers possessing two to three at-risk GST genotypes exhibited a statistically significant increased risk of colorectal cancer compared with non-smokers (P = 0.0002). In this latter stratum, heavy smokers exhibited a >5-fold increased risk relative to never-smokers (odds ratio, 5.43; 95% confidence interval, 2.22-13.23). Subjects with one at-risk GST genotype displayed a statistically significant but weaker association with smoking. These findings suggest that GST gene polymorphisms influence interindividual susceptibility to smoking-associated colorectal cancer. Our data indicate an important role for GST enzymes in the detoxification of colorectal carcinogens in tobacco smoke.     

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium

BackgroundThe evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case–control studies from Europe and United States.Subjects and methodsWe harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500 000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking.ResultsA total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI >27.5 kg/m², compared with 22.6–25.0, 1.50; 95% confidence interval (CI) 0.76–2.96]. No association was suggested for tobacco smoking; men drinking >400 g of ethanol per week had an HR of 1.57 (95% CI 0.66–3.70), compared with abstainers.ConclusionsOur study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.