Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.     

Hormonal risk factors for endometrial cancer: modification by cigarette smoking (United States)

Objectives: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors. Methods: Using multivariate adjusted models we examined interview data from a population-based case–control study of Wisconsin women (n = 740 cases, n = 2372 controls). Results: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6–1.0) compared to never smokers. No clear dose–response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4–5.3) than among current smokers (OR = 2.8, 95% CI: 1.4–5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3–4.9) than among current smokers (OR = 2.7, 95% CI: 1.3–5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6–15.1) among never smokers and 2.5 (95% CI: 0.8–7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7–3.6) than current smokers (OR = 1.1, 95% CI: 0.4–3.1). There was no modifying effect of smoking on the risk associated with parity. Conclusion: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones.     

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 survival after breast cancer diagnosis

We examined whether a history of smoking is associated with an increased risk of death from any cause or from breast cancer, among women diagnosed with breast cancer. This was a prospective observational study among 5,056 women from the Nurses' Health Study with Stages I-III invasive breast cancer diagnosed between 1978 and 2002 and for whom we had information on smoking, and who were followed until January 2002 or death, whichever came first. Subjects were classified as current, former or never smokers based upon smoking status at the biennial questionnaire immediately preceding the breast cancer diagnosis. In multivariate-adjusted analyses, compared with never smokers, women who were current smokers had a 43% increased adjusted relative risk (RR) [95% confidence interval (95% CI): 1.24-1.65] of death from any cause. A strong linear gradient was observed with the number of cigarettes per day smoked, p-trend <0.0001; the RR (95% CI) for 1-14, 15-24 and 25 or more cigarettes per day was 1.27 (1.01-1.61), 1.30 (1.08-1.57) and 1.79 (1.47-2.19). In contrast, there was no association with current smoking and breast cancer death; the RR (95% CI) was 1.00 (0.83-1.19). Current and past smokers were more likely than never smokers to die from primary lung cancer, chronic obstructive pulmonary disease and other lung diseases. We conclude that a history of smoking increased mortality following diagnosis with breast cancer, but did not increase mortality from breast cancer.     

Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies

Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p<0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p<0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p<0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking.     

Active and passive smoking and the risk of breast cancer in women aged 36-45 years: a population based case-control study in the UK

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case-control study of breast cancer in women aged 36-45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72-1.73) for past smokers and RR of 1.19 (95% CI 0.72-1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64-1.25), in past smokers, RR of 1.09 (95% CI 0.75-1.56), or in current smokers, RR of 0.93 (95% CI 0.67-1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.     

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.      

A prospective study of smoking and risk of breast cancer in young adult women.

OBJECTIVES: To investigate the association between smoking and invasive breast cancers characterized by their estrogen receptor status in a large prospective study of mainly premenopausal women. METHODS: 112,844 women aged 25-42 years in 1989 were followed 10 years; questionnaire information on medical illnesses and risk factors was collected biennially and information on diet was collected in 1991 and 1995. During this period of follow-up (1,077,536 person-years), 1009 incident breast cancer cases were documented. RESULTS: In the multivariate-adjusted models, smoking status was not significantly related to overall breast cancer risk: compared with never smokers, the relative risks (RRs) were 1.18 [95% confidence interval (CI) 1.02-1.36] for past smokers and 1.12 (95% CI 0.92-1.37) for current smokers. Increasing duration of smoking before the first pregnancy was associated with a greater risk of breast cancer, although little increase was seen in the highest category: compared with never smokers, RRs were 1.42 (95% CI 1.10-1.83) for 15-19 years of smoking and 1.10 (95% CI 0.80-1.52) for >/=20 years of smoking (P for trend = 0.01). Smoking was related most strongly to the risk of estrogen receptor-positive breast cancers. For women who had smoked for >/=20 years, the RR of estrogen receptor-positive cancer was 1.37 (95% CI 1.07-1.74) and the RR of estrogen receptor-negative cancer was 1.04 (95% CI 0.71-1.53). For smoking before age 15, the RRs were 1.49 (95% CI 1.03-2.17) for estrogen receptor-positive cancer and 1.19 (95% CI 0.69-2.08) for estrogen receptor-negative cancer. CONCLUSIONS: Our results suggest that longer duration of smoking may be related to the risk of estrogen receptor-positive breast cancer but possibly less so for estrogen receptor-negative breast cancer.     

The Copenhagen case-control study of renal pelvis and ureter cancer: role of smoking and occupational exposures

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% CI: 1.0-6.7) and in combination with other types of tobacco (RR = 3.8; 95% CI: 1.3-11.5). Non-significantly increased relative risks were observed for pipe smokers (RR = 2.2; 95% CI: 0.1-97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.5; 95% CI: 0.4-21.2). A strong dose-effect (p less than 0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis-ureter tumors, with the heaviest smokers having an 8-fold risk. Comparison with the dose-effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis-ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% CI: 1.9-6.1), while stopping smoking (RR = 0.6; 95% CI: 0.3-1.1) and use of filter cigarettes (RR = 0.5; 95% CI: 0.3-0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% CI: 1.6-9.8), and for exposure to coal and coke (RR = 4.0; 95% CI: 1.2-13.6), asphalt and tar (RR = 5.5; 95% CI: 1.6-19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.     

Postmenopausal hormone therapy and lung cancer risk in the cancer prevention study II nutrition cohort.

BACKGROUND: Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status. METHODS: We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR). RESULTS: During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected. CONCLUSION: These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality.     

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

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

Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study

We examined the relationship of body mass index (BMI), diabetes and smoking to endometrial cancer risk in a cohort of 36 761 Norwegian women during 15.7 years of follow-up. In multivariable analyses of 222 incident cases of endometrial cancer, identified by linkage to the Norwegian Cancer Registry, there was a strong increase in risk with increasing BMI (P-trend <0.001). Compared to the reference (BMI 20-24 kg m(-2)), the adjusted relative risk (RR) was 0.53 (95% confidence interval (CI): 0.19-1.47) for BMI<20 kg m(-2), 4.28 (95% CI: 2.58-7.09) for BMI of 35-39 kg m(-2) and 6.36 (95% CI: 3.08-13.16) for BMI>or=40 kg m(-2). Women with known diabetes at baseline were at three-fold higher risk (RR 3.13, 95% CI: 1.92-5.11) than those without diabetes; women who reported current smoking at baseline were at reduced risk compared to never smokers (RR 0.55, 95% CI: 0.35-0.86). The strong linear positive association of BMI with endometrial cancer risk and a strongly increased risk among women with diabetes suggest that any increase in body mass in the female population will increase endometrial cancer incidence.     

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.     

The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers

Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1 polyglutamine repeat polymorphism and pre-diagnosis smoking habits for BRCA1 mutation carriers to determine if there was an interaction between smoking and AIB1 genotype. Multivariate Cox proportional hazards regression was used with 316 female BRCA1 mutation carriers to model breast cancer risk. Ever having smoked was associated with a decreased breast cancer risk [Hazard Ratio (HR) = 0.63, 95% CI, 0.47-0.87]. A dose-response relationship between number of pack-years smoked and breast cancer risk was also found for women who smoked <20 pack years of cigarettes (HR = 0.72, 95% CI, 0.52-1.00) and for women who smoked >/=20 pack years (HR = 0.41, 95% CI, 0.23-0.71; P for trend = 0.0007). Women with a 28 repeat allele for AIB1 had a significantly reduced risk of breast cancer (HR = 0.72, 95% CI, 0.51-1.00). Women who smoked >/=20 pack-years with a 28 repeat allele had an even greater reduced risk of breast cancer (HR = 0.19, 95% CI, 0.07-0.54) compared to women who were never smokers with no 28 allele. Since AIB1 appears to modulate the effect of endogenous hormones via the estrogen receptor, and smoking affects circulating hormone levels, these results support evidence that steroid hormones play an important role in breast carcinogenesis in BRCA1 mutation carriers, and suggest mechanisms for developing novel cancer prevention strategies for BRCA1 mutation carriers.     

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.     

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.     

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency questionnaires administered every 2 to 4 years starting in 1980. For the smoking analyses, 737 confirmed cases of epithelial ovarian cancer were identified and for the dietary aims, 507 cases were identified through June 1, 2004. RESULTS: Compared with never-smokers, neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors (n = 69; rate ratio [RR], past = 2.02 [95% confidence interval (CI), 1.15-3.55]; RR, current = 2.22 [95% CI, 1.16-4.24]). A modest inverse association between caffeine intake and ovarian cancer risk was observed (RR, top vs bottom quintile = 0.80; 95% CI, 0.60-1.07 [P = .03]), which was strongest for women who had never used either oral contraceptives (RR = 0.65; 95% CI, 0.46-0.92 [P for heterogeneity = .02]) or postmenopausal hormones (RR = 0.57; 95% CI, 0.36-0.91 [P for heterogeneity = .13]). Alcohol was not associated with ovarian cancer risk. CONCLUSIONS: The results of the current study suggest that cigarette smoking may only increase the risk for mucinous ovarian tumors, and alcohol intake was not associated with risk. However, an inverse association was observed between caffeine intake and ovarian cancer risk, particularly in women not using hormones; this finding merits further study.     

Fruits, vegetables and lung cancer: a pooled analysis of cohort studies

Inverse associations between fruit and vegetable consumption and lung cancer risk have been consistently reported. However, identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies. We analyzed fruit and vegetable groups using standardized exposure and covariate definitions in 8 prospective studies. We combined study-specific relative risks (RRs) using a random effects model. In the pooled database, 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6-16 years across studies. Controlling for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p-value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79; 95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison, the association was weaker for total vegetable consumption (RR = 0.88; 95% CI = 0.78-1.00; p-value, test for trend = 0.12). Associations were similar between never, past, and current smokers. These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake. However, we cannot rule out the possibility that our results are due to residual confounding by smoking. The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation.     

Smoking and infectious agents and risk of in situ cervical cancer in Sydney, Australia

In a study of 116 in situ cervical cancer patients and 193 matched community controls in Sydney, Australia, smoking was found to be a major risk factor. Current smokers had a adjusted relative risk [RR] of 4.5 compared to nonsmokers [95% confidence interval (CI) 2.2-9.1] and exsmokers a RR of 1.3 [95% CI 0.6-3.0]. There was a stepwise dose-response relationship between risk and number of cigarettes smoked (30+ cigarettes/day, RR = 5.1, 95% CI 1.5-17.3); this dose-response relationship was more marked among current smokers. Years of cigarette smoking was not consistently related to risk. Exposures to herpes simplex virus type 2 and cytomegalovirus as measured by antibody prevalence were unrelated to risk (RR = 1.1 for both measures). However, cases appeared to have more exposure than controls to herpes simplex virus type 1 (RR = 2.3, 95% CI 1.1-4.4).