Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: a Prospective Study and Meta-Analysis

This work was supported by the French National Cancer Institute (INCa SHSESP17, grant No. 2017-127 to N. Murphy). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska degrees ne and V_asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment¼1.17 [95% confidence interval¼1.00 to 1.38]; odds ratioquartile4-quartile1¼1.33 [95% confidence interval¼0.89 to 1.97], Ptrend¼.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the doseresponse meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
French National Cancer Institute (INCa SHSESP17) 2017-127
World Health Organization
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
Danish Cancer Society
Ligue Contre le Cancer (France)
Institut Gustave Roussy (France)
Mutuelle Generale de l'Education Nationale (France)
Institut National de la Sante et de la Recherche Medicale (Inserm)
Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam Rehbruecke (DIfE) (Germany)
Federal Ministry of Education & Research (BMBF)
Fondazione AIRC per la ricerca sul cancro
Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR)
Netherlands Government
World Cancer Research Fund International (WCRF)
Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain) Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology-ICO (Spain)
Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden)
Cancer Research UK 14136 C8221/A29017 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1