Abstract 6452: A plasma metabolomic signature of healthy lifestyles and risk of colorectal cancer in the UK Biobank

Abstract

Abstract Background: Lifestyle factors contribute to the etiology of colorectal cancer (CRC). We aimed to derive a metabolomic signature of adherence to healthy lifestyles and examine its association with CRC risk. Methods: In the analysis, we included 98,898 UK Biobank participants with 168 metabolomic biomarkers measured by nuclear magnetic resonance spectroscopy from baseline plasma samples. A healthy lifestyle score (HLS) was derived from 8 lifestyle factors according to the American Cancer Society (ACS) guidelines. We applied elastic net regularized regressions to identify a metabolomic signature from 130 biomarkers. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of metabolomic signature with CRC risk after adjusting for known confounders. Results: During a median follow-up time of 8.2 years, 818 incident primary CRC cases were identified after participants were enrolled for more than two years. We observed a strong partial correlation between the metabolomic signature and HLS (r = 0.34), as well as waist-to-hip ratio, sedentary time, red and processed meat intake, and tobacco smoking aspects of the HLS (r = 0.14-0.33). A higher HLS was characterized by a signature of increased levels of linoleic acid, total cholines, and polyunsaturated fatty acids and decreased levels of omega-6 fatty acids, phospholipids in intermediate-density lipoprotein, and phosphatidylcholines. The metabolomic signature showed a significantly inverse association with CRC risk (HR = 0.84; 95% CI = 0.80-0.89 per standard deviation increment). The significantly inverse associations were observed irrespective of sex, educational attainment, and CRC subsite. Stronger associations were seen among participants aged between 50 and 60 years at study enrollment, and those diagnosed with CRC at 60 years old or later. Conclusion: We identified a metabolomic signature characterizing adherence to the ACS guidelines and showed that the signature was inversely associated with CRC risk. Citation Format: Fangcheng Yuan, Danxia Yu, Wanqing Wen, Wei Zheng. A plasma metabolomic signature of healthy lifestyles and risk of colorectal cancer in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6452.