Alaina M Bever1,2, Dong Hang3,4, Xiaosheng He5,6, Amit D Joshi1,5, Ming Ding3, Kana Wu1,5, Andrew T Chan5,7,8, Edward L Giovannucci3,7,9, Mingyang Song10,11,12. 1. Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA. 2. Harvard Medical School, Boston, MA, USA. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, China. 5. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. 6. Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 7. Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 8. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. 9. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 10. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. msong@hsph.harvard.edu. 11. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. msong@hsph.harvard.edu. 12. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. msong@hsph.harvard.edu.
Abstract
BACKGROUND: Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown. AIMS: Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors. METHODS: We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps. RESULTS: For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79). CONCLUSION: Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.
BACKGROUND: Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown. AIMS: Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors. METHODS: We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps. RESULTS: For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79). CONCLUSION: Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.
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Authors: David Jarvis; Jonathan S Mitchell; Philip J Law; Kimmo Palin; Sari Tuupanen; Alexandra Gylfe; Ulrika A Hänninen; Tatiana Cajuso; Tomas Tanskanen; Johanna Kondelin; Eevi Kaasinen; Antti-Pekka Sarin; Jaakko Kaprio; Johan G Eriksson; Harri Rissanen; Paul Knekt; Eero Pukkala; Pekka Jousilahti; Veikko Salomaa; Samuli Ripatti; Aarno Palotie; Heikki Järvinen; Laura Renkonen-Sinisalo; Anna Lepistö; Jan Böhm; Jukka-Pekka Meklin; Nada A Al-Tassan; Claire Palles; Lynn Martin; Ella Barclay; Susan M Farrington; Maria N Timofeeva; Brian F Meyer; Salma M Wakil; Harry Campbell; Christopher G Smith; Shelley Idziaszczyk; Timothy S Maughan; Richard Kaplan; Rachel Kerr; David Kerr; Daniel D Buchanan; Aung K Win; John L Hopper; Mark A Jenkins; Noralane M Lindor; Polly A Newcomb; Steve Gallinger; David Conti; Fred Schumacher; Graham Casey; Jussi Taipale; Lauri A Aaltonen; Jeremy P Cheadle; Malcolm G Dunlop; Ian P Tomlinson; Richard S Houlston Journal: Br J Cancer Date: 2016-06-23 Impact factor: 9.075