Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps.

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. PREVENTION RELEVANCE: 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.

• Authors: Michael N Passarelli, Bonne M Thompson, Jeffrey G McDonald, Dale C Snover, Thomas J Palys, Judy R Rees, Elizabeth L Barry, John A Baron
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 14 Issue 4 Pg. 479-488 (04 2021) ISSN: 1940-6215 [Electronic] United States
• PMID: 33408073 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Biomarkers
• Hydroxycholesterols
• Vitamins
• Vitamin D
• 27-hydroxycholesterol

Topics

• Adenoma (blood, drug therapy, epidemiology, pathology)
• Biomarkers (blood)
• Colonic Polyps (blood, drug therapy, epidemiology, pathology)
• Colorectal Neoplasms (blood, drug therapy, epidemiology, pathology)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Hydroxycholesterols (blood)
• Male
• Middle Aged
• Prognosis
• Risk Factors
• United States (epidemiology)
• Vitamin D (administration & dosage)
• Vitamins (administration & dosage)