Dong Hang1,2, Xiaosheng He3,4, Ane Sørlie Kværner5, Andrew T Chan3,6,7, Kana Wu2, Shuji Ogino7,8,9,10, Zhibin Hu1, Hongbing Shen1, Edward L Giovannucci2,6,10, Mingyang Song11,12,13. 1. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China. 2. Department of Nutrition, Harvard T.H. Chan School of Public Health, 667 Huntington Avenue, Kresge 906A, Boston, MA, 02115, USA. 3. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 4. Department of Colorectal Surgery, The Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 5. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. 6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 7. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. 8. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. 9. Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA. 10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 11. Department of Nutrition, Harvard T.H. Chan School of Public Health, 667 Huntington Avenue, Kresge 906A, Boston, MA, 02115, USA. mingyangsong@mail.harvard.edu. 12. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. mingyangsong@mail.harvard.edu. 13. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. mingyangsong@mail.harvard.edu.
Abstract
BACKGROUND: Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. METHODS: We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend = 0.03, respectively). CONCLUSIONS: The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.
BACKGROUND: Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. METHODS: We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend = 0.03, respectively). CONCLUSIONS: The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.
Entities:
Keywords:
Biomarker; Colorectal cancer; Molecular epidemiology; Premalignancy; Sex difference
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