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A Metabolomic Signature of Obesity and Risk of Colorectal Cancer: Two Nested Case-Control Studies.
Pubmed ID
36837854 (View this publication on the PubMed website)
Digital Object Identifier
Metabolites. 2023 Feb 5; Volume 13 (Issue 2)
Yang M, Zhu C, Du L, Huang J, Lu J, Yang J, Tong Y, Zhu M, Song C, Shen C, Dai J, Lu X, Xu Z, Li N, Ma H, Hu Z, Gu D, Jin G, Hang D, Shen H
  • Department of Epidemiology, School of Public Health, Southeast University, Nanjing 210009, China.
  • Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China.
  • Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China.
  • Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
  • Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Obesity is a leading contributor to colorectal cancer (CRC) risk, but the metabolic mechanisms linking obesity to CRC are not fully understood. We leveraged untargeted metabolomics data from two 1:1 matched, nested case-control studies for CRC, including 223 pairs from the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and 190 pairs from a prospective Chinese cohort. We explored serum metabolites related to body mass index (BMI), constructed a metabolomic signature of obesity, and examined the association between the signature and CRC risk. In total, 72 of 278 named metabolites were correlated with BMI after multiple testing corrections (p FDR < 0.05). The metabolomic signature was calculated by including 39 metabolites that were independently associated with BMI. There was a linear positive association between the signature and CRC risk in both cohorts (p for linear < 0.05). Per 1-SD increment of the signature was associated with 38% (95% CI: 9-75%) and 28% (95% CI: 2-62%) higher risks of CRC in the US and Chinese cohorts, respectively. In conclusion, we identified a metabolomic signature for obesity and demonstrated the association between the signature and CRC risk. The findings offer new insights into the underlying mechanisms of CRC, which is critical for improved CRC prevention.

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