TY - JOUR
T1 - Circulating 27-hydroxycholesterol and risk of colorectal adenomas and serrated polyps
AU - Passarelli, Michael N.
AU - Thompson, Bonne M.
AU - McDonald, Jeffrey G.
AU - Snover, Dale C.
AU - Palys, Thomas J.
AU - Rees, Judy R.
AU - Barry, Elizabeth L.
AU - Baron, John A.
N1 - Funding Information:
This work was supported by the National Cancer Institute at the NIH (R01CA098286, to JA. Baron), National Heart, Lung, and Blood Institute at the NIH (P01HL020948, to J.G. McDonald), and National Institute of General Medical Sciences at the NIH (P20GM104416, to M.N. Passarelli). On behalf of the Polyp Prevention Study Group, the authors express their appreciation to the study participants, investigators, and staff. We thank Leila A. Mott for supporting data management and Margaret R. Karagas for direction of the Center for Molecular Epidemiology and Biorepository Core at Dartmouth.
Funding Information:
This work was supported by the National Cancer Institute at the NIH (R01CA098286, to JA. Baron), National Heart, Lung, and Blood Institute at the NIH (P01HL020948, to J.G. McDonald), and National Institute of General Medical Sciences at the NIH (P20GM104416, to M.N. Passarelli).
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-20-0414
DO - 10.1158/1940-6207.CAPR-20-0414
M3 - Article
C2 - 33408073
AN - SCOPUS:85103862866
SN - 1940-6207
VL - 14
SP - 479
EP - 488
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 4
ER -