Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses
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Niki Dimou... [et al.]. Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses. Cancer Epidemiol Biomarkers Prev 1 September 2022; 31 (9): 1839–1848. [https://doi.org/10.1158/1055-9965.EPI-21-1176]
SponsorshipWorld Health Organization; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London; NIHR Imperial Biomedical Research Centre (BRC); Danish Cancer Society; Ligue Contre le Cancer (France) Institut Gustave Roussy (France) MutuelleGenerale de l'Education Nationale (France); Institut National de la Sante et de la Recherche Medicale (Inserm); Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany) Federal Ministry of Education & Research (BMBF); Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR); Netherlands Government Netherlands Government; World Cancer Research Fund International (WCRF); Netherlands Government; Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain); Junta de Andalucia; Principality of Asturias Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden); Cancer Research UK 14136 C8221/A29017; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 1000143 MR/M012190/1 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/ 1; Cancer Research UK C864/A14136 C18281/A29019; Cancer Research UK C864/A14136 C18281/A29019
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 twosampleMR analyses, genetic variants robustly associated with lifetime amount of smoking (n ¼ 126 variants) and ever having smoked regularly (n ¼ 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.