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Davenport et al 1 underscored the urgent need to identify new modifiable factors for colorectal adenomas. A few studies2 3 reported that higher yogurt intake may reduce the risk of colorectal cancer (CRC), potentially mediated by the gut microbiome. However, no study has yet evaluated the association between yogurt intake and precursors of CRC.
We prospectively evaluated the association between yogurt intake and risk of conventional adenoma and serrated lesion, among 32 606 men in the Health Professionals Follow-up Study (HPFS) and 55 743 women in the Nurses’ Health Study (NHS), who have undergone lower endoscopy between 1986 and 2012. These participants provided detailed information on demographics, lifestyle and diet including yogurt consumption every 4 years. Multivariable logistic regressions were used to calculate ORs and 95% CIs associated with cumulative average of yogurt intake. We examined the associations by adenoma type (conventional adenomas only, serrated lesions only or both), malignant potential (for conventional adenomas: high-risk (≥1 cm or with villous component or high grade/severe dysplasia, or ≥3 adenomas) vs low risk; for serrated lesions: ≥1 vs <1 cm) and anatomical site (proximal, distal or rectum).
We documented 5811 adenomas in men and 8116 adenomas in women. In men, compared with individuals without yogurt consumption, men who consumed ≥2 servings/week had a lower risk of conventional adenoma (multivariable OR=0.81, 95% CI=0.71 to 0.94, ptrend=0.01; table 1). This inverse association was more pronounced for adenomas with high malignant potential (OR=0.74, 95% CI=0.59 to 0.92, ptrend=0.01) than those with low risk (ptrend=0.25) (figure 1A). Also, stronger inverse associations were observed for colon (OR=0.82, 95% CI=0.70 to 0.95, ptrend=0.01) than for rectal adenomas (ptrend=0.95) (figure 1B). Overall, among men, no apparent association was observed for serrated lesions (ptrend=0.34), but a trend toward inverse association for lesions ≥1 cm was seen (OR=0.48, 95% CI=0.25 to 0.95, ptrend=0.04) (figure 1A). In women, no associations were observed for conventional adenomas and/or serrated lesions (table 1) or according to adenoma subtype or anatomical sites (online supplementary table S1).
Supplementary file 1
Yogurt has been recommended by the Dietary Guidelines for Americans as part of fat-free and low-fat dairy4; however, its intake is low. We found that yogurt intake may reduce risk of conventional adenoma, in particular those of high malignant potential, and independent of calcium and non-yogurt dairy intake. We also reported the probable inverse association with risk of large serrated lesions, an emerging clinical phenotype that also requires extensive surveillance. Taking together, yogurt may help prevent precursors of CRC, potentially through both adenoma-to-carcinoma sequence and serrated pathway. A number of possible mechanisms have been postulated. Products of the two common probiotics used in yogurt, Lactobacillus bulgaricus and Streptococcus thermophilus, may reduce levels of carcinogens such as nitroreductase, faecal activated bacterial enzymes and soluble faecal bile acids.5–7 The stronger link between yogurt intake and colon versus rectal adenomas may in part due to the lower pH in the colon, which is more hospitable for probiotics.8 Yogurt may also reduce adenoma risk by exerting anti-inflammatory effects on colon mucosa and ameliorating gut barrier dysfunction.9 As male patients with adenoma present with increased gut permeability,10yogurt may benefit more for men compared with women.
The strengths of the study include prospective and updated assessments of yogurt intake with large number of cases of conventional adenomas and serrated lesions. Future studies in different racial/ethnical groups are warranted to confirm these findings and elucidate underlying biological mechanisms associated with sex and anatomical site differences.
We thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. State cancer registries: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming.
YC and XZ contributed equally.
Contributors XiZ, YC and XuZ had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: XiZ, YC, XuZ. Acquisition of data: KW, MS, ATC, ELG, YC. Analysis and interpretation of data: all coauthors. Drafting of the manuscript: XiZ, YC, XuZ. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: XiZ, YC. Obtained funding: SO, ATC, ELG, XuZ. Administrative, technical or material support: YC, XuZ. Study supervision: YC, XuZ.
Funding Grant support: The Health Professionals Follow-up Study and Nurses’ Health Study were supported by the National Institutes of Health (NIH) grants UM1CA186107, P50CA127003, P01CA87969 and UM1CA167552. This work was additional funded by NIH grants (R03 CA197879 and R21 CA222940 to KW, R21 CA230873 to KW and SO, R01 CA151993 and R35 CA197735 to SO; K24 DK098311 to ATC; K07 CA218377 to YC; K07 CA188126 to XuZ). XiZ is supported by International Programme for PhD Candidates, Sun Yat-Sen University. KW is supported by an Investigator Initiated Grants from the American Institute for Cancer Research. SO is supported by Nodal Award from the Dana-Farber Harvard Cancer Center and by grants from the Project P Fund for Colorectal Cancer Research, the Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance and American Association for Cancer Research (Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant). ATC is a Stuart and Suzanne Steele MGH Research Scholar. XuZ is also supported by the American Cancer Society Research Scholar Grant (RSG NEC-130476) and Boston Nutrition Obesity Research Center Pilot and Feasibility Award.
Competing interests Charles S. Fuchs reports consulting role for Agios, Bain Capital, Bayer, Celgene, Dicerna, Five Prime Therapeutics, Gilead Sciences, Eli Lilly, Entrinsic Health, Genentech, KEW, Merck, Merrimack Pharmaceuticals, Pfizer, Sanofi, Taiho, and Unum Therapeutics. He also serves as a Director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health.
Provenance and peer review Not commissioned; internally peer reviewed.
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