{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:53:18Z","timestamp":1791402798255,"version":"4.3.3"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NCI Intramural Research Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human studies investigating the prospective relationship between microbial metabolites and colorectal cancer (CRC) risk are lacking. We tested whether higher serum bile acids (BAs) and lower short-chain fatty acids (SCFAs) were associated with CRC risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In baseline serum collected more than 30\u2009years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry\u00a0 assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n\u2009=\u2009262 cases; women: n\u2009=\u2009233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n\u2009=\u2009598 cases). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for BA and SCFA quartiles and summary measures with CRC overall and by anatomic location using multivariable conditional logistic regression models. PLCO analyses were stratified by sex. All statistical tests were 2-sided.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1\u2009=\u20092.85, 95% CI\u2009=\u20091.45 to 5.60, Qtrend\u2009=\u20090.011), glycodeoxycholic (OR Q4 v Q1\u2009=\u20093.45, 95% CI\u2009=\u20091.79 to 6.64, Qtrend\u2009=\u20090.006), taurodeoxycholic (OR Q4 v Q1\u2009=\u20092.36, 95% CI\u2009=\u20091.22 to 4.55, Qtrend\u2009=\u20090.023), and glycolithocholic acid (ORQ4 v Q1\u2009=\u20092.71, 95% CI\u2009=\u20091.41 to 5.22, Qtrend\u2009=\u20090.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR\u2009=\u20090.55, 95% CI\u2009=\u20090.31 to 0.98, Ptrend\u2009=\u2009.03). Associations for total BAs and SCFAs were strongest among women with proximal colon cancer. No statistically significant associations were observed for BA or SCFA measures among men.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jncics\/pkac027","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T19:13:23Z","timestamp":1648581203000},"source":"Crossref","is-referenced-by-count":29,"title":["Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-8748","authenticated-orcid":false,"given":"Erikka","family":"Loftfield","sequence":"first","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National 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National Institutes of Health, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn","family":"Hullings","sequence":"additional","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Murphy","sequence":"additional","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health, Rockville, MD, 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