Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps
Open Access
- 6 January 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 14 (4), 479-488
- https://doi.org/10.1158/1940-6207.capr-20-0414
Abstract
The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05–1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17–3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66–1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50–2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps. This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.Keywords
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Funding Information
- NCI (R01CA098286)
- NIH (P01HL020948)
- NIH (P20GM104416)
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