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- Title
Plasma metabolomic profiles for colorectal cancer precursors in women.
- Authors
Hang, Dong; Zeleznik, Oana A.; Lu, Jiayi; Joshi, Amit D.; Wu, Kana; Hu, Zhibin; Shen, Hongbing; Clish, Clary B.; Liang, Liming; Eliassen, A. Heather; Ogino, Shuji; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Song, Mingyang
- Abstract
How metabolome changes influence the early process of colorectal cancer (CRC) development remains unknown. We conducted a 1:2 matched nested case–control study to examine the associations of pre-diagnostic plasma metabolome (profiled using LC–MS) with risk of CRC precursors, including conventional adenomas (n = 586 vs. 1141) and serrated polyps (n = 509 vs. 993), in the Nurses' Health Study (NHS) and NHSII. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We used the permutation-based Westfall and Young approach to account for multiple testing. Subgroup analyses were performed for advanced conventional adenomas (defined as at least one adenoma of ≥ 10 mm or with high-grade dysplasia, or tubulovillous or villous histology) and high-risk serrated polyps that were located in the proximal colon or with size of ≥ 10 mm. After multiple testing correction, among 207 metabolites, higher levels of C36:3 phosphatidylcholine (PC) plasmalogen were associated with lower risk of conventional adenomas, with the OR (95% CI) comparing the 90th to the 10th percentile of 0.62 (0.48–0.81); C54:8 triglyceride (TAG) was associated with higher risk of serrated polyps (OR = 1.79, 95% CI: 1.31–2.43), and phenylacetylglutamine (PAG) was associated with lower risk (OR = 0.57, 95% CI:0.43–0.77). PAG was also inversely associated with advanced adenomas (OR = 0.57, 95% CI: 0.36–0.89) and high-risk serrated polyps (OR = 0.54, 95% CI: 0.32–0.89), although the multiple testing-corrected p value was > 0.05. Our findings suggest potential roles of lipid metabolism and phenylacetylglutamine, a microbial metabolite, in the early stage of colorectal carcinogenesis, particularly for the serrated pathway.
- Subjects
COLORECTAL cancer; METABOLOMICS; CANCER patients; POLYPS; ODDS ratio; LIPID metabolism; MICROBIAL metabolites
- Publication
European Journal of Epidemiology, 2022, Vol 37, Issue 4, p413
- ISSN
0393-2990
- Publication type
Article
- DOI
10.1007/s10654-021-00834-5