. 2018 Jun;118(12):1639-1647.

doi: 10.1038/s41416-018-0108-8. Epub 2018 May 24.

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

Sonja Neumeyer¹, Barbara L Banbury², Volker Arndt³, Sonja I Berndt⁴, Stephane Bezieau⁵, Stephanie A Bien², Dan D Buchanan^{6

7}, Katja Butterbach¹, Bette J Caan⁸, Peter T Campbell⁹, Graham Casey¹⁰, Andrew T Chan^{11

12

13}, Stephen J Chanock⁴, James Y Dai², Steven Gallinger¹⁴, Edward L Giovannucci^{12

15

16

17}, Graham G Giles^{7

18}, William M Grady^{19

20}, Jochen Hampe²¹, Michael Hoffmeister³, John L Hopper⁷, Li Hsu², Mark A Jenkins⁷, Amit Joshi^{13

15}, Susanna C Larsson²², Loic Le Marchand²³, Annika Lindblom^{24

25}, Victor Moreno^{26

27}, Mathieu Lemire²⁸, Li Li²⁹, Yi Lin², Kenneth Offit³⁰, Polly A Newcomb², Paul D Pharaoh³¹, John D Potter², Lihong Qi³², Gad Rennert^{33

34

35}, Clemens Schafmayer³⁶, Robert E Schoen³⁷, Martha L Slattery³⁸, Mingyang Song^{11

13

16}, Cornelia M Ulrich³⁹, Aung K Win^{7

40}, Emily White², Alicja Wolk^{22

41}, Michael O Woods⁴², Anna H Wu⁴³, Stephen B Gruber⁴⁴, Hermann Brenner^{3

45

46}, Ulrike Peters², Jenny Chang-Claude^{47

48}

Affiliations

¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
² Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98124, USA.
³ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-9776, USA.
⁵ Centre Hospitalier Universitaire (CHU), Nantes Service de Génétique Médicale, 44093, Nantes, France.
⁶ Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁸ Division of Research, Kaiser Permanente Medical Care Program of Northern California, Oakland, 94612, CA, USA.
⁹ Epidemiology Research Program, American Cancer Society, Atlanta, GA, 30329-4251, USA.
¹⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
¹¹ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02115, USA.
¹² Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
¹³ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA.
¹⁴ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1 X 5, Canada.
¹⁵ Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁶ Department of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁷ Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
¹⁸ Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3010, Australia.
¹⁹ Department of Medicine, Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
²⁰ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
²¹ Medical Department 1, University Hospital Dresden, TU Dresden, 01307, Dresden, Germany.
²² Institute of Environmental Medicine, Karolinska Institutet Solna, SE-171 77, Stockholm, Sweden.
²³ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, 96822, HI, USA.
²⁴ Department of Clinical Genetics, Karolinska University Hospital Solna, SE-171 77, Stockholm, Sweden.
²⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet Solna, SE-171 77, Stockholm, Sweden.
²⁶ Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08028, Barcelona, Spain.
²⁷ CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain and University of Barcelona, Barcelona, 08007, Spain.
²⁸ Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
²⁹ Department of Family Medicine and Community Health, Case Western Reserve University, Cleveland, OH, 44106, USA.
³⁰ Department of Medicine, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
³¹ Centre for Cancer Genetic Epidemiology, Department of Public Health & Primary Care, University of Cambridge, Cambridge, CB2 8AR, UK.
³² Department of Public Health Sciences, University of California, Davis, CA, 95817, USA.
³³ Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³⁴ Clalit Health Services National Israeli Cancer Control Center, Haifa, 34361, Israel.
³⁵ Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, 34361, Israel.
³⁶ Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, 24118, Kiel, Germany.
³⁷ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
³⁸ Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, 84108, USA.
³⁹ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
⁴⁰ Genetic Medicine and Familial Cancer Centre, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
⁴¹ Department of Surgical Sciences, Uppsala University, Uppsala, SE-171 77, Sweden.
⁴² Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1C 5S7, Canada.
⁴³ Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁴⁴ Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁴⁵ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany.
⁴⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
⁴⁷ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. j.chang-claude@dkfz-heidelberg.de.
⁴⁸ Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, 20246, Hamburg, Germany. j.chang-claude@dkfz-heidelberg.de.

PMID: 29795306
PMCID: PMC6008474
DOI: 10.1038/s41416-018-0108-8

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

Sonja Neumeyer et al. Br J Cancer. 2018 Jun.

. 2018 Jun;118(12):1639-1647.

doi: 10.1038/s41416-018-0108-8. Epub 2018 May 24.

Authors

Affiliations

¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
² Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98124, USA.
³ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-9776, USA.
⁵ Centre Hospitalier Universitaire (CHU), Nantes Service de Génétique Médicale, 44093, Nantes, France.
⁶ Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁸ Division of Research, Kaiser Permanente Medical Care Program of Northern California, Oakland, 94612, CA, USA.
⁹ Epidemiology Research Program, American Cancer Society, Atlanta, GA, 30329-4251, USA.
¹⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
¹¹ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02115, USA.
¹² Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
¹³ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02115, USA.
¹⁴ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1 X 5, Canada.
¹⁵ Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁶ Department of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁷ Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
¹⁸ Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3010, Australia.
¹⁹ Department of Medicine, Division of Gastroenterology, University of Washington School of Medicine, Seattle, WA, 98195, USA.
²⁰ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
²¹ Medical Department 1, University Hospital Dresden, TU Dresden, 01307, Dresden, Germany.
²² Institute of Environmental Medicine, Karolinska Institutet Solna, SE-171 77, Stockholm, Sweden.
²³ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, 96822, HI, USA.
²⁴ Department of Clinical Genetics, Karolinska University Hospital Solna, SE-171 77, Stockholm, Sweden.
²⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet Solna, SE-171 77, Stockholm, Sweden.
²⁶ Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), 08028, Barcelona, Spain.
²⁷ CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain and University of Barcelona, Barcelona, 08007, Spain.
²⁸ Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
²⁹ Department of Family Medicine and Community Health, Case Western Reserve University, Cleveland, OH, 44106, USA.
³⁰ Department of Medicine, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
³¹ Centre for Cancer Genetic Epidemiology, Department of Public Health & Primary Care, University of Cambridge, Cambridge, CB2 8AR, UK.
³² Department of Public Health Sciences, University of California, Davis, CA, 95817, USA.
³³ Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³⁴ Clalit Health Services National Israeli Cancer Control Center, Haifa, 34361, Israel.
³⁵ Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, 34361, Israel.
³⁶ Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, 24118, Kiel, Germany.
³⁷ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
³⁸ Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, 84108, USA.
³⁹ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, 84112, USA.
⁴⁰ Genetic Medicine and Familial Cancer Centre, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
⁴¹ Department of Surgical Sciences, Uppsala University, Uppsala, SE-171 77, Sweden.
⁴² Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1C 5S7, Canada.
⁴³ Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁴⁴ Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁴⁵ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany.
⁴⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
⁴⁷ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. j.chang-claude@dkfz-heidelberg.de.
⁴⁸ Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, 20246, Hamburg, Germany. j.chang-claude@dkfz-heidelberg.de.

PMID: 29795306
PMCID: PMC6008474
DOI: 10.1038/s41416-018-0108-8

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

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

Affiliations

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

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Abstract

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