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

3 Citations (Scopus)

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

Fingerprint

Menarche
Random Allocation
Menopause
Colorectal Neoplasms
Single Nucleotide Polymorphism
Estrogens
Odds Ratio
Confidence Intervals
Gonadal Steroid Hormones
Body Mass Index
Logistic Models
Hormones

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Neumeyer, S., Banbury, B. L., Arndt, V., Berndt, S. I., Bezieau, S., Bien, S. A., ... 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

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

In: British Journal of Cancer, Vol. 118, No. 12, 01.06.2018, p. 1639-1647.

Research output: Contribution to journalArticle

Neumeyer, S, Banbury, BL, Arndt, V, Berndt, SI, Bezieau, S, Bien, SA, Buchanan, DD, Butterbach, K, Caan, BJ, Campbell, PT, Casey, G, Chan, AT, Chanock, SJ, Dai, JY, Gallinger, S, Giovannucci, EL, Giles, GG, Grady, WM, Hampe, J, Hoffmeister, M, Hopper, JL, Hsu, L, Jenkins, MA, Joshi, A, Larsson, SC, Le Marchand, L, Lindblom, A, Moreno, V, Lemire, M, Li, L, Lin, Y, Offit, K, Newcomb, PA, Pharaoh, PD, Potter, JD, Qi, L, Rennert, G, Schafmayer, C, Schoen, RE, Slattery, ML, Song, M, Ulrich, CM, Win, AK, White, E, Wolk, A, Woods, MO, Wu, AH, Gruber, SB, Brenner, H, Peters, U & 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, vol. 118, no. 12, pp. 1639-1647. https://doi.org/10.1038/s41416-018-0108-8
Neumeyer, Sonja ; Banbury, Barbara L. ; Arndt, Volker ; Berndt, Sonja I. ; Bezieau, Stephane ; Bien, Stephanie A. ; Buchanan, Dan D. ; Butterbach, Katja ; Caan, Bette J. ; Campbell, Peter T. ; Casey, Graham ; Chan, Andrew T. ; Chanock, Stephen J. ; Dai, James Y. ; Gallinger, Steven ; Giovannucci, Edward L. ; Giles, Graham G. ; Grady, William M. ; Hampe, Jochen ; Hoffmeister, Michael ; Hopper, John L. ; Hsu, Li ; Jenkins, Mark A. ; Joshi, Amit ; Larsson, Susanna C. ; Le Marchand, Loic ; Lindblom, Annika ; Moreno, Victor ; Lemire, Mathieu ; Li, Li ; Lin, Yi ; Offit, Kenneth ; Newcomb, Polly A. ; Pharaoh, Paul D. ; Potter, John D. ; Qi, Lihong ; Rennert, Gad ; Schafmayer, Clemens ; Schoen, Robert E. ; Slattery, Martha L. ; Song, Mingyang ; Ulrich, Cornelia M. ; Win, Aung K. ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Wu, Anna H. ; Gruber, Stephen B. ; Brenner, Hermann ; Peters, Ulrike ; Chang-Claude, Jenny. / Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. In: British Journal of Cancer. 2018 ; Vol. 118, No. 12. pp. 1639-1647.
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title = "Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer",
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.",
author = "Sonja Neumeyer and Banbury, {Barbara L.} and Volker Arndt and Berndt, {Sonja I.} and Stephane Bezieau and Bien, {Stephanie A.} and Buchanan, {Dan D.} and Katja Butterbach and Caan, {Bette J.} and Campbell, {Peter T.} and Graham Casey and Chan, {Andrew T.} and Chanock, {Stephen J.} and Dai, {James Y.} and Steven Gallinger and Giovannucci, {Edward L.} and Giles, {Graham G.} and Grady, {William M.} and Jochen Hampe and Michael Hoffmeister and Hopper, {John L.} and Li Hsu and Jenkins, {Mark A.} and Amit Joshi and Larsson, {Susanna C.} and {Le Marchand}, Loic and Annika Lindblom and Victor Moreno and Mathieu Lemire and Li Li and Yi Lin and Kenneth Offit and Newcomb, {Polly A.} and Pharaoh, {Paul D.} and Potter, {John D.} and Lihong Qi and Gad Rennert and Clemens Schafmayer and Schoen, {Robert E.} and Slattery, {Martha L.} and Mingyang Song and Ulrich, {Cornelia M.} and Win, {Aung K.} and Emily White and Alicja Wolk and Woods, {Michael O.} and Wu, {Anna H.} and Gruber, {Stephen B.} and Hermann Brenner and Ulrike Peters and Jenny Chang-Claude",
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T1 - Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

AU - Neumeyer, Sonja

AU - Banbury, Barbara L.

AU - Arndt, Volker

AU - Berndt, Sonja I.

AU - Bezieau, Stephane

AU - Bien, Stephanie A.

AU - Buchanan, Dan D.

AU - Butterbach, Katja

AU - Caan, Bette J.

AU - Campbell, Peter T.

AU - Casey, Graham

AU - Chan, Andrew T.

AU - Chanock, Stephen J.

AU - Dai, James Y.

AU - Gallinger, Steven

AU - Giovannucci, Edward L.

AU - Giles, Graham G.

AU - Grady, William M.

AU - Hampe, Jochen

AU - Hoffmeister, Michael

AU - Hopper, John L.

AU - Hsu, Li

AU - Jenkins, Mark A.

AU - Joshi, Amit

AU - Larsson, Susanna C.

AU - Le Marchand, Loic

AU - Lindblom, Annika

AU - Moreno, Victor

AU - Lemire, Mathieu

AU - Li, Li

AU - Lin, Yi

AU - Offit, Kenneth

AU - Newcomb, Polly A.

AU - Pharaoh, Paul D.

AU - Potter, John D.

AU - Qi, Lihong

AU - Rennert, Gad

AU - Schafmayer, Clemens

AU - Schoen, Robert E.

AU - Slattery, Martha L.

AU - Song, Mingyang

AU - Ulrich, Cornelia M.

AU - Win, Aung K.

AU - White, Emily

AU - Wolk, Alicja

AU - Woods, Michael O.

AU - Wu, Anna H.

AU - Gruber, Stephen B.

AU - Brenner, Hermann

AU - Peters, Ulrike

AU - Chang-Claude, Jenny

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41416-018-0108-8

DO - 10.1038/s41416-018-0108-8

M3 - Article

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VL - 118

SP - 1639

EP - 1647

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

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