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.     

Cigarette and alcohol consumption and the risk of colorectal cancer in Shanghai, China.

The relation of cigarette smoking and alcohol drinking to colorectal cancer risk has been inconsistent in the epidemiological literature. In a population-based case-control study of colorectal cancer in Shanghai, China, where the incidence rates are rising sharply, we examined the association with tobacco and alcohol use. Cases were aged 30-74 years and newly diagnosed with cancers of the colon (N = 931) or rectum (N = 874) between 1990 and 1992. Controls (N = 1552) were randomly selected among Shanghai residents, frequency-matched to cases by gender and age. Information on lifetime consumption of tobacco and alcohol, as well as demographic and other risk factors, was obtained through in-person interviews. Associations with cigarette smoking and alcohol use were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Among women, the prevalence of smoking and alcohol drinking was low, and no significant association with colon or rectal cancer was observed. Although cigarette smoking among men was not related overall to colon or rectal cancer risk, there was a 50% excess risk of rectal cancer (OR 1.5, 95% CI 0.9-2.5) among those who smoked 55 or more pack-years. Among men, former alcohol drinkers had an increased risk of colon cancer (OR 2.3, 95% CI 1.4-3.7) but not rectal cancer, while current drinkers had a 30-50% excess risk of colon cancer only among those with long-term (30+ years) and heavy (>560 g ethanol/week) consumption. The excess risks were mainly associated with hard liquor consumption, with no material difference in risk between proximal and distal colon cancer. Although cigarette smoking and alcohol drinking in general were not risk factors for colorectal cancers in Shanghai, there were small excess risks for rectal cancer among heavy smokers and colon cancer among heavy drinkers.     

Cigarette smoking and risk of prostate cancer in the physicians' health study (United States)

To assess whether cigarette smoking is associated with prostate cancer incidence or mortality, we analyzed a large cohort of 22,071 men, aged 40-84 at baseline, in the Physicians' Health Study. During an average of 12.5 years of follow-up, we documented 996 cases of prostate cancer, including 113 fatal cases. Men were categorized according to smoking status, total pack-years smoked, and duration of smoking. We used Cox proportional hazard models to estimate the relative risks associated with smoking. Compared to never smokers, the age-adjusted relative risks (RR) of total prostate cancer were 1. 14 (95% confidence interval [CI] = 1.00-1.30) for past smokers, 1.10 (95% CI = 0.78-1.55) for current smokers of less than 20 cigarettes per day, and 1.10 (95% CI = 0.84-1.44) for current smokers of 20 or more cigarettes per day. Adjustment for body mass index, height, alcohol intake, and physical activity did not materially alter these findings. No significant association was observed in analyses of total pack-years smoked or duration of smoking. The results were similar for non-fatal and fatal prostate cancer. These data indicate no material association between cigarette smoking and prostate cancer incidence or mortality.     

Cigarette smoking and survival after ovarian cancer diagnosis.

We have examined the association between cigarette smoking and ovarian cancer survival in 676 women with invasive epithelial ovarian cancer, recruited into a case-control study in the early 1990s. Information about cigarette smoking and other personal and reproductive factors was obtained from a personal interview at the time of diagnosis. Cox proportional hazards models were used to evaluate the association between cigarette smoking and time to ovarian cancer death. Current smokers at diagnosis were more likely to die early than women who had never smoked [adjusted hazard ratio (HR), 1.36; 95% confidence interval (95% CI), 1.01-1.84]. Increased risks of dying were greater among those who had accumulated more pack-years of smoking (HR for 30+ pack-years compared with never smokers, 1.94; 95% CI, 1.41-2.66) and smoked more cigarettes per day (HR, 1.93; 95% CI, 1.37-2.73). All these associations were stronger among women with late-stage disease (HR for current versus never smokers, 1.58; 95% CI, 1.15-2.18). Time since quitting had little effect on survival after adjusting for lifetime smoking exposure. These results validate and extend recent findings and suggest that premorbid cigarette smoking is related to worse outcome in ovarian cancer patients.     

Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths

Liver cancer and liver cirrhosis are common causes of death in China, where chronic lifelong hepatitis B infection is a major cause of both diseases. To help determine whether smoking is a cofactor for the development of liver cancer, we ascertained retrospectively the smoking habits of 36,000 adults who had died from liver cancer (cases) and 17,000 who had died from cirrhosis (controls) in 24 Chinese cities and 74 rural counties. Calculations of the smoker vs. nonsmoker risk ratios (RR) for liver cancer mortality were standardised for age and locality. Among adult men (aged 35+) there was a 36% excess risk of death from liver cancer among smokers (smoker vs. nonsmoker standardised risk ratio [RR] =1.36, with 95% confidence interval [CI] 1.29-1.43, 2p<0.00001; attributable fraction 18%). In the general male population this indicates absolute risks of death from liver cancer before age 70 of about 4% in smokers and 3% in nonsmokers (in the absence of other causes). Most liver cancer, however, occurs among the 10-12% of men with haematological evidence of chronic hepatitis B infection, so among them the corresponding risks would be about 33% in smokers and 25% in nonsmokers. The RR was approximately independent of age, was similar in urban and rural areas, was not significantly related to the age when smoking started but was significantly (p<0.001) greater for cigarette smokers than for smokers of other forms of tobacco. Among men who smoked only cigarettes, the RR was significantly (p<0.001 for trend) related to daily consumption, with a greater hazard among those who smoked 20/day (RR 1.50, 95% CI 1.39-1.62) than among those who smoked fewer (mean 10/day: RR=1.32, 95% CI 1.23-1.41). Smoking was also associated with a significant excess of liver cancer death in women (RR 1.17, 95% CI 1.06-1.29, 2p=0.003; attributable fraction 3%), but fewer women (17%) than men (62%) were smokers, and their cigarette consumption per smoker was lower. Among women who smoked only cigarettes, there was a significantly greater hazard among those who smoked at least 20/day (mean 22/day: RR=1.45, 95% CI 1.18-1.79) than among those who smoked fewer (mean 8/day: RR=1.09, 95% CI 0.94-1.25). These associations indicate that tobacco is currently responsible for about 50,000 liver cancer deaths each year in China, chiefly among men with chronic HBV infection.     

Cigarette smoking and the risk of gastric cancer: a pooled analysis of two prospective studies in Japan

To examine the association between cigarette smoking and the risk of gastric cancer, we conducted a pooled analysis of 2 population-based prospective cohort studies in rural northern Japan. Cohort 1 included 9,980 men (>or=40 years old) and Cohort 2 included 19,412 men (40-64 years old). The subjects completed a self-administered questionnaire on cigarette smoking and other health habits. We identified 228 cases of gastric cancer among Cohort 1 subjects (9 years of follow-up with 74,073 person-years) and 223 among Cohort 2 subjects (7 years of follow-up with 141,675 person-years). From each cohort, we computed the relative risk (RR) and 95% confidence interval (CI) of gastric cancer associated with smoking using a Cox regression analysis and pooled these estimates to obtain summary measures. The pooled multivariate RRs (95% CIs) for current smokers and past smokers compared to subjects who had never smoked were 1.84 (1.39-2.43) and 1.77 (1.29-2.43), respectively. The higher number of cigarettes smoked per day among current smokers was associated with a linear increase in risk (trend p < 0.05). The significant increase in risk for past smokers remained for up to 14 years after cessation. An increased risk was noted for cancer of the antrum but not for cardia or body lesions. The risk was increased for both differentiated and nondifferentiated histologic subtypes. Our findings support the hypothesis that cigarette smoking is a risk factor for gastric cancer.     

Smoking and bladder cancer in Spain: effects of tobacco type, timing, environmental tobacco smoke, and gender.

We examined the effects of dose, type of tobacco, cessation, inhalation, and environmental tobacco smoke exposure on bladder cancer risk among 1,219 patients with newly diagnosed bladder cancer and 1,271 controls recruited from 18 hospitals in Spain. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between bladder cancer risk and various characteristics of cigarette smoking. Current smokers (men: OR, 7.4; 95% CI, 5.3-10.4; women: OR, 5.1; 95% CI, 1.6-16.4) and former smokers (men: OR, 3.8; 95% CI, 2.8-5.3; women: OR, 1.8; 95% CI, 0.5-7.2) had significantly increased risks of bladder cancer compared with nonsmokers. We observed a significant positive trend in risk with increasing duration and amount smoked. After adjustment for duration, risk was only 40% higher in smokers of black tobacco than that in smokers of blond tobacco (OR, 1.4; 95% CI, 0.98-2.0). Compared with risk in current smokers, a significant inverse trend in risk with increasing time since quitting smoking blond tobacco was observed (> or =20 years cessation: OR, 0.2; 95% CI, 0.1-0.9). No trend in risk with cessation of smoking black tobacco was apparent. Compared with men who inhaled into the mouth, risk increased for men who inhaled into the throat (OR, 1.7; 95% CI, 1.1-2.6) and chest (OR, 1.5; 95% CI, 1.1-2.1). Cumulative occupational exposure to environmental tobacco smoke seemed to confer increased risk among female nonsmokers but not among male nonsmokers. After eliminating the effect of cigarette smoking on bladder cancer risk in our study population, the male-to-female incidence ratio decreased from 8.2 to 1.7, suggesting that nearly the entire male excess of bladder cancer observed in Spain is explained by cigarette smoking rather than occupational/environmental exposures to other bladder carcinogens.     

Cigarette smoking and testicular cancer.

The purpose of this study was to determine the relation between testicular cancer and cigarette smoking. Data were collected between 1995 and 1996 in Ontario, Canada, as part of the Enhanced Cancer Surveillance Study. Pack-years and years of smoking were examined among all subjects (212 cases and 252 controls) and former and current smokers. Years since quitting and age at smoking initiation were examined among former and current smokers only. Independent of smoking status, significant associations were noted among those who smoked between 12 and 24 pack-years [odds ratio (OR) = 1.96 (95% confidence interval (CI): 1.04-3.69), relative to nonsmokers] or greater [>24 pack-years, OR = 2.31 (95% CI: 1.12-4.77), relative to nonsmokers], and among those who smoked >21 years [OR = 3.18 (95% CI: 1.32-7.64), relative to nonsmokers]. Quitting smoking was not found to result in a reduction of risk. No association was observed for smoking at adolescence relative to a later period. Results from the study suggest that cigarette smoking exerts an adverse influence on testicular cancer risk that is not mitigated by smoking cessation and not altered by age at initiation.     

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.     

Associations between smoking, passive smoking, GSTM-1, NAT2, and rectal cancer.

Cigarette smoking has been identified as a risk factor for colon cancer, however, much less is known about the association between cigarette smoking and rectal cancer. The purpose of this article is to evaluate the associations between rectal cancer and active and passive cigarette smoking and other forms of tobacco use. We also evaluate how genetic variants of GSTM-1 and NAT2 alter these associations. A population-based case-control study of 952 incident rectal cancer cases and 1205 controls was conducted. Detailed tobacco use information was collected as part of an interviewer-administered questionnaire. DNA was extracted from blood to examine genetic variants of GSTM-1 and NAT2. Cigarette smoking was associated with an increased risk of rectal cancer in men [odds ratio (OR)=1.5, 95% confidence interval (CI), 1.1-2.1 for current smokers; OR=1.7, 95% CI, 1.3-2.3 for smoking >20 pack-years of cigarettes relative to never-smokers]. After adjusting for active smoking, exposure to cigarette smoke of others also was associated with increased risk among men (OR=1.5, 95% CI, 1.1-2.0). Neither GSTM-1 genotype nor NAT2-imputed phenotype was independently associated with rectal cancer. However, the risk associated with smoking cigarettes among those who were GSTM-1 null relative to those who never smoked and had the GSTM-1 present genotype was OR=2.0 (95% CI, 1.2-3.3). This interaction was of borderline significance (P=0.08). Men who had the combined GSTM-1 present genotype and who were rapid acetylators had no increased risk from cigarette smoking. There were no significant associations between cigarette smoking and rectal cancer among women. This study shows that men who smoke cigarettes, especially those who smoke >20 pack-years, are at increased risk of rectal cancer. This association may be influenced by GSTM-1 genotype. Furthermore, exposure to cigarette smoke of others may increase risk of rectal cancer among men who do not smoke.     

Cigarette smoking and the risk of colorectal cancer in women

Colorectal cancer incidence rates for smokers, nonsmokers living with smokers (i.e., passive smokers), and nonsmokers in smoke-free households were compared in a 12-year prospective study of 25,369 women who participated in a private census conducted in Washington County, MD, in 1963. Women who smoked had a decreased relative risk of colorectal cancer compared with the risk for nonsmokers (age-adjusted relative risk, 0.76; 95% confidence interval, 0.52-1.10). The risk for passive smokers was similar to that for smokers. The relative risks were significantly reduced for older women; relative risks were 0.42 for smokers and 0.66 for passive smokers over age 65. The data suggest that older women who smoke have a lower risk of colorectal cancer than nonsmokers. The effect may be mediated by an antiestrogenic effect of smoking.     

Smoking and mortality from esophageal cancer in China: a large case-control study of 19,734 male esophageal cancer deaths and 104,846 living spouse controls

An innovative population-based case-control study was conducted in a national mortality survey to assess the hazards of tobacco use on esophageal cancer among Chinese men. Cases were 19,734 males aged 35 years or older, who died of esophageal cancer during 1986-1988. Controls were 104,846 male living spouses of the same age when their wife died (of any cause) during the same period in the same county or city. The absolute esophageal cancer death rates were higher in smokers than those in nonsmokers in all geographical groups. The relative risks for esophageal cancer were 1.88 (95% CI: 1.73-2.05) and 1.39 (95% CI: 1.28-1.50) in urban and rural men, respectively, after adjustment for other relevant covariates including age group (5 years) and locality. When the calculation was restricted to men aged 35-69, the risk ratios for current cigarette smokers increased significantly with increasing number of cigarettes smoked daily and duration of smoking. Tobacco use, in any form, is an important risk factor for esophageal cancer in Chinese men. Selecting living spouses as controls is a unique and useful approach in the design of case-control studies of cigarette smoking.     

Cigarette smoking and colorectal carcinoma mortality in a cohort with long-term follow-up

BACKGROUND: Evidence suggests that colorectal carcinoma (CRC) may be a tobacco-associated malignancy. METHODS: In the current study, the authors examined the association between cigarette smoking and CRC mortality in the Chicago Heart Association Detection Project in Industry study, a cohort of 39,299 men and women with an average of 26 years of follow-up. To assess whether the association was stronger in participants with a potentially long history of smoking, the authors also stratified the analysis using a baseline age > or = 50 years versus < 50 years. RESULTS: Using multivariate Cox regression analysis, there was a marginally significant trend (P = 0.06) for men and women combined between smoking and CRC mortality. In the age-stratified analysis in the older participant group, there was no apparent association for men, women, or men and women combined. In the younger participant group, there appeared to be dose-response relations for women and for men and women combined (P value for trend = 0.008 and 0.03, respectively) between smoking and CRC mortality. The relative risk for women who smoked >20 cigarettes/day compared with never smokers was 2.49 (95% confidence interval [95% CI], 0.87-7.12), and was 1.87 for men and women combined (95% CI, 1.08-3.22). CONCLUSIONS: The results of the current study support an association between cigarette smoking and CRC mortality, particularly in women age < 50 years.     

Association between cigarette smoking and colorectal cancer in the Women's Health Initiative

The evidence linking cigarette smoking to the risk of colorectal cancer is inconsistent. We investigated the associations between active and passive smoking and colorectal cancer among 146,877 Women's Health Initiative participants. Women reported detailed smoking histories at enrollment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between smoking and overall and site-specific risk of colorectal cancer. Invasive colorectal cancer was diagnosed in 1242 women over an average of 7.8 years (range = 0.003-11.2 years) of follow-up. In adjusted analyses, statistically significant positive associations were observed between most measures of cigarette smoking and risk of invasive colorectal cancer. Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with colorectal cancer in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer.     

Lung cancer and cigarette smoking in women: a multicenter case-control study in Europe

The association between cigarette smoking and lung cancer risk in women was investigated within the framework of a case-control study in 9 centres from 6 European countries. Cases were 1,556 women up to 75 years of age with histologically confirmed primary lung cancer; 2, 450 controls with age distribution similar to cases were selected. The predominant cell type was adenocarcinoma (33.5%), with similar proportions for squamous-cell type (26.4%) and small-cell carcinoma (22.3%). Overall, smoking cigarettes at any time was associated with a 5-fold increase in lung cancer risk (odds ratio 5.21, 95% confidence interval 4.49-6.04); corresponding figures for current smoking habits were 8.94, 7.54-10.6. The association showed a dose-response relationship with duration of the habit and daily and cumulative lifetime smoking. A significant excess risk of 70% was associated with every 10 pack-years smoked. After 10 years of smoking cessation, the relative risk decreased to 20% compared to current smokers. The following characteristics were associated with a higher relative risk: inhalation of smoke, smoking non-filter cigarettes, smoking dark-type cigarettes and starting at young age. The association was observed for all major histological types, being the strongest for small-cell type carcinoma, followed by squamous-cell type and the lowest for adenocarcinoma. The proportion of lung-cancer cases in the population attributable to cigarette smoking ranged from 14% to 85%. We concluded that women share most features of the association between cigarette smoking and lung cancer observed in men.     

Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use

Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk; we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among individuals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (P(interaction) = 0.05): relative to current NSAID users who never smoked, individuals who had both smoked for >40 years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8; 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use.     

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.     

Should we consider gallbladder cancer a new smoking-related cancer? A comprehensive meta-analysis focused on dose–response relationships

The few studies on the association of smoking with gallbladder cancer risk have given conflicting results. Here, we provide the most accurate and up-to-date quantification of the effect of cigarette smoking on gallbladder cancer risk, and investigate for the first time the dose–response relationships. Using an innovative approach for the identification of publications, we conducted a systematic review and meta-analysis of epidemiological studies published until March 2019 on the association of smoking with gallbladder cancer risk. Pooled relative risks (RRs) for smoking were estimated using random-effects models; one-stage random-effects log-linear models were used for dose–response relationships. Out of 22 eligible articles, 20 (11 case–control and 9 cohort studies) were included in the meta-analysis, for a total of 4,676 gallbladder cancer cases. Compared to never smokers, the pooled RR was 1.33 (95% confidence interval [CI]: 1.17–1.51) for current and 1.07 (95% CI: 0.94–1.23) for former smokers. The risk of gallbladder cancer increased linearly with smoking intensity and duration, the RR being 1.60 (95% CI: 1.21–2.11) for 30 cigarettes/day and 1.25 (95% CI: 1.01–1.56) for 30 years of smoking. There was a nonsignificant linear decrease in gallbladder cancer risk with increasing time since quitting, compared to current smokers. Former smokers reached the risk of those who had never smoked 20 years after quitting. This comprehensive meta-analysis suggests a moderately but significantly higher risk of gallbladder cancer for current but not former smokers. We also provide the first report of a linear increase in gallbladder cancer risk according to smoking intensity and duration.     

Cigarette smoking and risk of glioma: a prospective cohort study

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. N-nitroso compounds are known carcinogens, which are found in cigarette smoke and can induce gliomas in rats. On this basis, it has been hypothesized that cigarette smoking may be associated with an increased risk of glioma. We investigated the association between cigarette smoking and glioma risk in the National Breast Screening Study, which included 89,835 Canadian women aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and risk of glioma. During a mean of 16.4 years of follow-up, we observed 120 incident glioma cases. Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an increase in risk. When the association with former smokers was further examined by years since quitting, women who had quit smoking >10 years before baseline were at a decreased risk of glioma compared with women who had quit within the 10 years prior to baseline (HR = 0.55, 95% CI = 0.29-1.07), indicating that the association between former smokers and glioma may be driven by women, who recently quit smoking. Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack-years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest. The present study provides some support for a positive association between cigarette smoking and risk of glioma.