Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses

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  • Niki Dimou, International Agency for Research on Cancer, Lyon, France., France
  • Wemimo Omiyale, University of Oxford, United Kingdom
  • Carine Biessy, International Agency for Research on Cancer, Lyon, France., France
  • Vivian Viallon, International Agency for Research on Cancer, Lyon, France., France
  • Rudolf Kaaks, Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany., Germany
  • Tracy A O'Mara, QIMR Berghofer Med Res Inst, QIMR Berghofer Medical Research Institute, Dept Genet & Computat Biol, Australia
  • Elom K Aglago, International Agency for Research on Cancer, Lyon, France., France
  • Eva Ardanaz, Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain., Spain
  • Manuela M Bergmann, German Institute of Human Nutrition Potsdam-Rehbrücke, Germany
  • Nicola P Bondonno, Danish Cancer Society, Denmark
  • Tonje Braaten, UiT Arctic Univ Norway, UiT The Arctic University of Tromso, Inst Arctic & Marine Biol, Norway
  • Sandra M Colorado-Yohar, CIBER - Center for Biomedical Research Network, Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain., National Faculty of Public Health, University of Antioquia, Medellín, Spain
  • Marta Crous-Bou, L'Hospitalet de Llobregat, Barcelona, Harvard T.H. Chan School of Public Health, Boston, MA, Spain
  • Christina C Dahm
  • Renée T Fortner, Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany., Germany
  • Inger T Gram, UiT Arctic Univ Norway, UiT The Arctic University of Tromso, Inst Arctic & Marine Biol, Norway
  • Sophia Harlid, Umeå University, Sweden
  • Alicia K Heath, Imperial College London, United Kingdom
  • Annika Idahl, Umeå University, Sweden
  • Marina Kvaskoff, Inserm, CESP, U1018, Villejuif, France9Université of Paris-Sud, UMRS 1018, Villejuif, France., France
  • Therese H Nøst, UiT Arctic Univ Norway, UiT The Arctic University of Tromso, Inst Arctic & Marine Biol, Norwegian University of Science and Technology, Norway
  • Kim Overvad
  • Domenico Palli, Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy., Italy
  • Aurora Perez-Cornago, The University of Oxford, United Kingdom
  • Carlotta Sacerdote, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Italy
  • Maria-Jose Sánchez, Escuela Andaluza de Salud Pública (EASP), Granada, Instituto de Investigación Biosanitaria (ibs.GRANADA), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), University of Granada, Spain
  • Matthias B Schulze, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany., University of Potsdam, Germany
  • Gianluca Severi, Inserm, CESP, U1018, Villejuif, France9Université of Paris-Sud, UMRS 1018, Villejuif, France., University of Florence, France
  • Vittorio Simeon, University of Naples "L. Vanvitelli", Italy
  • Giovanna Tagliabue, Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian 1, Milan, Italy
  • Anne Tjønneland, Folkesundhed København, Denmark
  • Thérèse Truong, Inserm, CESP, U1018, Villejuif, France9Université of Paris-Sud, UMRS 1018, Villejuif, France., France
  • Rosario Tumino, Hyblean Association for Epidemiological Research (AIRE -ONLUS), Italy
  • Mattias Johansson, International Agency for Research on Cancer, Lyon, France., France
  • Elisabete Weiderpass, Office of the Director, International Agency For Research On Cancer.
  • ,
  • Neil Murphy, International Agency for Research on Cancer, Lyon, France., France
  • Marc J Gunter, International Agency for Research on Cancer, Lyon, France.
  • ,
  • Ben Lacey, The University of Oxford, United Kingdom
  • Naomi E Allen, The University of Oxford, United Kingdom
  • Laure Dossus, International Agency for Research on Cancer, Lyon, France., France

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.

Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume31
Issue9
Pages (from-to)1839-1848
Number of pages10
ISSN1055-9965
DOIs
Publication statusPublished - Sep 2022

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