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Background: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses., Methods: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined., Results: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer., Conclusions: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer., Impact: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk., (©2022 The Authors; Published by the American Association for Cancer Research.)

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45-75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993-1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status., Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident., Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Smoking has recently been established as a risk factor for rectal cancer. We examined whether the smoking-related increase in rectal cancer differed by gender. Methods: We followed 602,242 participants (49% men), aged 19 to 67 years at enrollment from four Norwegian health surveys carried out between 1972 and 2003, by linkage to Norwegian national registries through December 2007. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazard models and adjusting for relevant confounders. Heterogeneity by gender in the effect of smoking and risk of rectal cancer was tested with Wald χ². Results: During a mean follow-up of 14 years, 1,336 men and 840 women developed invasive rectal cancer. Ever smokers had a significantly increased risk of rectal cancer of more than 25% for both men (HR = 1.27, 95% CI = 1.11-1.45) and women (HR = 1.28, 95% CI = 1.11-1.48) compared with gender-specific never smokers. Men smoking =20 pack-years had a significantly increased risk of rectal cancer of 35% (HR = 1.35, 95% CI = 1.14-1.58), whereas for women, it was 47% (HR = 1.47, 95% CI = 1.13-1.91) compared with gender-specific never smokers. For both men and women, we observed significant dose-response associations between the risk of rectal cancer for four variables [Age at smoking initiation in years (both ptrend <0.05), number of cigarettes smoked per day (both ptrend <0.0001), smoking duration in years (ptrend <0.05, <0.0001) and number of pack-years smoked (both ptrend <0.0001)]. The test for heterogeneity by gender was not significant between smoking status and the risk of rectal cancer (Wald χ², p -value; current smokers = 0.85; former smokers = 0.87; ever smokers = 1.00). Conclusions: Smoking increases the risk of rectal cancer to the same extent in women as in men. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality overall and by subsite in a large Norwegian cohort. Methods: We followed 602,242 participants from four Norwegian health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints. Results: During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06-1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ2=0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ2=0.02 and χ2=0.04, respectively). Conclusion: Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively. [ABSTRACT FROM AUTHOR]