Abstract 756: The association between serum serine and glycine and related-metabolites with pancreatic cancer in two prospective cohort studies

Abstract Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine, glycine and their related-metabolites with pancreatic cancer risk. Methods. Two parallel nested case-control studies derived from the Shanghai Cohort Study (with 129 cases and 258 controls) and from the Singapore Chinese Health Study (with 58 cases and 104 controls), respectively, were conducted to examine these associations. Conditional logistic regression method was used to evaluate the associations between serine, glycine and related-matabolites with pancreatic cancer risk, adjusting for potential confounders (i.e., level of education, body mass index, smoking status, alcohol consumption, history of diabetes, serum cotinine concentration, serum pyridoxal 5'-phosphate concentration (PLP), and estimated glomerular filtration rate (eGFR)). Results. In the two studies combined data, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of serine and glycine were 0.42 (0.23-0.78) and 0.39 (0.21-0.72), respectively, compared with the lowest quartile. No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The novel observation for a statistically significant inverse association for serum serine and glycine with risk of pancreatic cancer supports a protective role of these metabolites in the folate pathway against the development of pancreatic cancer in humans. With the experimental data showing the impact of serine and glycine on gut microbiota composition, [YJM1] our findings suggest that the alteration of gut microbiota may play a contributing role in reducing the risk of pancreatic cancer. Funding: The Singapore Chinese Health Study was supported by the National Institutes of Health (NIH) of the United States (grants # R01 CA144034 and UM1 CA182876). HN Luu was partially supported by the University of Pittsburgh Medical Center Hillman Cancer Center start-up grant. P Paragomi was supported by the NIH T32CA186873 training grant in cancer epidemiology and prevention. W-P Koh was partially supported by the National Medical Research Council, Singapore (NMRC/CSA/0055/2013). Citation Format: Hung N. Luu, Renwei Wang, Pedram Paragomi, Joyce Y. Huang, Lesley M. Butler, Øivind Midttun, Arve Ulvik, Aizhen Jin, Yu-Tang Gao, Per M. Ueland, Woon-Puay Koh, Jian-Min Yuan. The association between serum serine and glycine and related-metabolites with pancreatic cancer in two prospective cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 756.