TY - JOUR

T1 - Cigarette Smoking and Endometrial Cancer Risk

T2 - Observational and Mendelian Randomization Analyses

AU - Dimou, Niki

AU - Omiyale, Wemimo

AU - Biessy, Carine

AU - Viallon, Vivian

AU - Kaaks, Rudolf

AU - O'Mara, Tracy A.

AU - Aglago, Elom K.

AU - Ardanaz, Eva

AU - Bergmann, Manuela M.

AU - Bondonno, Nicola P.

AU - Braaten, Tonje

AU - Colorado-Yohar, Sandra M.

AU - Crous-Bou, Marta

AU - Dahm, Christina C.

AU - Fortner, Renee T.

AU - Gram, Inger T.

AU - Harlid, Sophia

AU - Heath, Alicia K.

AU - Idahl, Annika

AU - Kvaskoff, Marina

AU - Nost, Therese H.

AU - Overvad, Kim

AU - Palli, Domenico

AU - Perez-Cornago, Aurora

AU - Sacerdote, Carlotta

AU - Sanchez, Maria-Jose

AU - Schulze, Matthias B.

AU - Severi, Gianluca

AU - Simeon, Vittorio

AU - Tagliabue, Giovanna

AU - Tjonneland, Anne

AU - Truong, Therese

AU - Tumino, Rosario

AU - Johansson, Mattias

AU - Weiderpass, Elisabete

AU - Murphy, Neil

AU - Gunter, Marc J.

AU - Lacey, Ben

AU - Allen, Naomi E.

AU - Dossus, Laure

PY - 2022

Y1 - 2022

N2 - Background: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. How-ever, 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.

AB - Background: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. How-ever, 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.

KW - GENETIC-VARIANTS

KW - SEX-HORMONES

KW - IDENTIFICATION

KW - REGRESSION

KW - ESTROGENS

KW - OVERLAP

KW - OBESITY

KW - BREAST

KW - WOMEN

KW - INDEX

U2 - 10.1158/1055-9965.EPI-21-1176

DO - 10.1158/1055-9965.EPI-21-1176

M3 - Journal article

C2 - 35900194

VL - 31

SP - 1839

EP - 1848

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 9

ER -