Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

Sonja Neumeyer, Barbara L. Banbury, Volker Arndt, Sonja I. Berndt, Stephane Bezieau, Stephanie A. Bien, Dan D. Buchanan, Katja Butterbach, Bette J. Caan, Peter T. Campbell, Graham Casey, Andrew T. Chan, Stephen J. Chanock, James Y. Dai, Steven Gallinger, Edward L. Giovannucci, Graham G. Giles, William M. Grady, Jochen Hampe, Michael HoffmeisterJohn L. Hopper, Li Hsu, Mark A. Jenkins, Amit Joshi, Susanna C. Larsson, Loic Le Marchand, Annika Lindblom, Victor Moreno, Mathieu Lemire, Li Li, Yi Lin, Kenneth Offit, Polly A. Newcomb, Paul D. Pharaoh, John D. Potter, Lihong Qi, Gad Rennert, Clemens Schafmayer, Robert E. Schoen, Martha L. Slattery, Mingyang Song, Cornelia M. Ulrich, Aung K. Win, Emily White, Alicja Wolk, Michael O. Woods, Anna H. Wu, Stephen B. Gruber, Hermann Brenner, Ulrike Peters, Jenny Chang-Claude

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. Methods: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. Results: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. Conclusions: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

Original languageEnglish (US)
Pages (from-to)1639-1647
Number of pages9
JournalBritish Journal of Cancer
Volume118
Issue number12
DOIs
StatePublished - Jun 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Neumeyer, S., Banbury, B. L., Arndt, V., Berndt, S. I., Bezieau, S., Bien, S. A., Buchanan, D. D., Butterbach, K., Caan, B. J., Campbell, P. T., Casey, G., Chan, A. T., Chanock, S. J., Dai, J. Y., Gallinger, S., Giovannucci, E. L., Giles, G. G., Grady, W. M., Hampe, J., ... Chang-Claude, J. (2018). Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. British Journal of Cancer, 118(12), 1639-1647. https://doi.org/10.1038/s41416-018-0108-8