Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case–Control Study and Meta-Analysis
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Justin Harbs... [et al.]. Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case–Control Study and Meta-Analysis. Cancer Epidemiol Biomarkers Prev 1 April 2022; 31 (4): 793–803. [https://doi.org/10.1158/1055-9965.EPI-21-0996]
SponsorshipCancer foundation in Northern Sweden AMP 17-856 AMP 18-915 AMP 19-967; Lions Cancer Research Fund in Northern Sweden LP 20-2227; Department of Radiation Sciences, Umea University; NIHR Imperial Biomedical Research Centre (BRC); Danish Cancer Society; Ligue nationale contre le cancer; IARC; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London; Institut Gustave Roussy, MutuelleGenerale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (Inserm); Deutsche Krebshilfe; Helmholtz Association; German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE); Federal Ministry of Education & Research (BMBF); Fondazione AIRC per la ricerca sul cancro; Compagnia di San Paolo; Consiglio Nazionale delle Ricerche (CNR); Netherlands Government Netherlands Government; World Cancer Research Fund International (WCRF); Netherlands Government; Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII) (Spain); Junta de Andalucia; Principality of Asturias; 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 Region of Skane (Sweden) Region of Vasterbotten (Sweden); Cancer Research UK 14136 C8221/A29017 UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission 1000143 MR/M012190/1; Swedish Research Council; European Commission VR 2017-00650
Background: Endogenous sex hormonesmay contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking. Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) andtheNorthern SwedenHealth and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men. Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL ¼ 0.98; 95% CI, 0.96–1.00; I2 ¼ 22%] and free testosterone (RR per 1 ng/dL ¼ 0.98; 95% CI, 0.95–1.00; I2 ¼ 0%). Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development. Impact: Additional support for the involvement of sex hormones in male colon cancer.