Long H Nguyen1, Yin Cao2, Jinhee Hur3, Raaj S Mehta1, Daniel R Sikavi4, Yiqing Wang1, Wenjie Ma1, Kana Wu3, Mingyang Song5, Edward L Giovannucci6, Eric B Rimm6, Walter C Willett6, Wendy S Garrett7, Jacques Izard8, Curtis Huttenhower9, Andrew T Chan10. 1. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 2. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St Louis, Missouri; Alvin J. Siteman Cancer Center, Washington University School of Medicine in St. Louis, St Louis, Missouri; Division of Gastroenterology, Washington University School of Medicine in St. Louis, St Louis, Missouri. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 5. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 7. Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts. 8. Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska; Nebraska Food for Health Center, University of Nebraska, Lincoln, Nebraska; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska. 9. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Electronic address: chuttenh@hsph.harvard.edu. 10. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Electronic address: achan@partners.org.
Abstract
BACKGROUND & AIMS: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
BACKGROUND & AIMS: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
Authors: Eleni Linos; Walter C Willett; Eunyoung Cho; Graham Colditz; Lindsay A Frazier Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-07-31 Impact factor: 4.254
Authors: Oleg K Glebov; Luz M Rodriguez; Kenneth Nakahara; Jean Jenkins; Janet Cliatt; Casey-Jo Humbyrd; John DeNobile; Peter Soballe; Richard Simon; George Wright; Patrick Lynch; Sherri Patterson; Henry Lynch; Steven Gallinger; Aby Buchbinder; Gary Gordon; Ernest Hawk; Ilan R Kirsch Journal: Cancer Epidemiol Biomarkers Prev Date: 2003-08 Impact factor: 4.254
Authors: Katharina Nimptsch; Vasanti S Malik; Teresa T Fung; Tobias Pischon; Frank B Hu; Walter C Willett; Charles S Fuchs; Shuji Ogino; Andrew T Chan; Edward Giovannucci; Kana Wu Journal: Int J Cancer Date: 2013-11-25 Impact factor: 7.396
Authors: Sonia S Maruti; Diane Feskanich; Helaine R Rockett; Graham A Colditz; Laura A Sampson; Walter C Willett Journal: Epidemiology Date: 2006-03 Impact factor: 4.822