TY - JOUR
T1 - The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors
AU - Nguyen, Long H.
AU - Cao, Yin
AU - Hur, Jinhee
AU - Mehta, Raaj S.
AU - Sikavi, Daniel R.
AU - Wang, Yiqing
AU - Ma, Wenjie
AU - Wu, Kana
AU - Song, Mingyang
AU - Giovannucci, Edward L.
AU - Rimm, Eric B.
AU - Willett, Walter C.
AU - Garrett, Wendy S.
AU - Izard, Jacques
AU - Huttenhower, Curtis
AU - Chan, Andrew T.
N1 - Funding Information:
Funding This work was supported by the National Institutes of Health (Nurses’ Health Study II cohort infrastructure grant of U01 CA176726, Loan Repayment Program, and K23 DK125838 to LHN; R37 CA246175, R21 AA027608, and K07 CA218377 to YC; R03 CA197879, R21 CA222940, and R21 CA230873 to KW; R00 CA215314 to MS; R01 CA202704 to WSG, JI, CH, and ATC; and R35 CA253185 to ATC), American Gastroenterological Association (Research Scholars Award to LHN), the Crohn’s and Colitis Foundation (Research Fellowship Award and Career Development Award to LHN and Senior Investigator Award to ATC), American Institute for Cancer Research (Investigator Initiated Grant to KW), American Cancer Society (Mentored Research Scholar Grant in Applied and Clinical Research to MS), Massachusetts General Hospital (Stuart and Suzanne Steele Research Scholar Award to ATC), Starr Cancer Consortium, and Cancer Research UK (Grand Challenge Award to WSG and CH), and United States Department of Agriculture National Institute (Food and Agriculture Hatch Multistate Research Capacity Funding Program grant W4122 to JI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health .
Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Cancer Biogeography
KW - Colorectal Adenoma
KW - Colorectal Carcinogenesis
KW - FFQ
KW - Hydrogen Sulfide
UR - http://www.scopus.com/inward/record.url?scp=85115385790&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2021.07.008
DO - 10.1053/j.gastro.2021.07.008
M3 - Article
C2 - 34273347
AN - SCOPUS:85115385790
VL - 161
SP - 1423-1432.e4
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 5
ER -