Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer
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. We used a Mendelian randomis...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 May 2018
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| In: |
British journal of cancer
Year: 2018, Volume: 118, Issue: 12, Pages: 1639-1647 |
| ISSN: | 1532-1827 |
| DOI: | 10.1038/s41416-018-0108-8 |
| Online Access: | Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1038/s41416-018-0108-8 Verlag, Pay-per-use, Volltext: https://www.nature.com/articles/s41416-018-0108-8 
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| Author Notes: | 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 Hoffmeister, John 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 |
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| 520 | |a 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. 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. 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. Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk. | ||
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