Skip to Main Content

An official website of the United States government

Government Funding Lapse

Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit  cc.nih.gov. Updates regarding government operating status and resumption of normal operations can be found at OPM.gov.

Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer.

About this Publication
Title
Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer.
Pubmed ID
35583137 (View this publication on the PubMed website)
Digital Object Identifier
Publication
JNCI Cancer Spectr. 2022 May 2; Volume 6 (Issue 3)
Authors
Loftfield E, Falk RT, Sampson JN, Huang WY, Hullings A, Murphy G, Weinstein SJ, Albanes D, Freedman ND, Sinha R
Affiliations
  • Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
  • Biostatistics Branch, DCEG, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Abstract

BACKGROUND: 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.

METHODS: In baseline serum collected more than 30 years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry  assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n = 262 cases; women: n = 233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n = 598 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.

RESULTS: In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1 = 2.85, 95% CI = 1.45 to 5.60, Qtrend = 0.011), glycodeoxycholic (OR Q4 v Q1 = 3.45, 95% CI = 1.79 to 6.64, Qtrend = 0.006), taurodeoxycholic (OR Q4 v Q1 = 2.36, 95% CI = 1.22 to 4.55, Qtrend = 0.023), and glycolithocholic acid (ORQ4 v Q1 = 2.71, 95% CI = 1.41 to 5.22, Qtrend = 0.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR = 0.55, 95% CI = 0.31 to 0.98, Ptrend = .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.

CONCLUSIONS: Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.

Related CDAS Studies
Related CDAS Projects