Abstract
BackgroundTryptophan metabolism is involved in esophageal carcinogenesis. However, its genetic mechanisms remain unclear. This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism on susceptibility to esophageal cancer (EC) and elucidate the mechanisms underlying genetic variation in EC progression. MethodsAge- and sex-matched cohorts of 167 patients with EC and 236 healthy controls were enrolled in this study. The concentrations of tryptophan and its metabolites were determined by self-assembled high-performance liquid chromatography-tandem mass spectrometry. High-throughput sequencing techniques were utilized to detect candidate coding genetic variants, and dominant genetic models were used to elucidate the genotypic associations. ResultsTryptophan metabolism was significantly imbalanced in patients with EC, with elevated indolepropionic acid (IPA) levels reducing the risk of EC susceptibility. ACSM2B rs73530508 (A > G) mutation was associated with higher IPA levels in vivo (P = 0.0004, false discovery rate [FDR] = 0.0092) and significantly reduced the risk of EC susceptibility (odds ratio [OR]: 0.576, Padj = 0.0161). Mediation effect analysis indicated that single-nucleotide polymorphism may inhibit carcinogenesis by reducing IPA metabolism and excretion with a mediation effect of 45.54%. ConclusionsThis study identifies the potential mechanism of ACSM2B rs73530508 (A > G) in esophageal carcinogenesis and its role in driving increased IPA levels, thereby suppressing the risk of development.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
