Impact of FTO Genetic Variants on Colorectal Cancer Risk: A Case–Control Study

This study aimed to assess the association between fat mass and obesity-associated ( FTO ) genetic variants and colorectal cancer (CRC) risk in a retrospective case–control cohort. FTO expression in CRC versus normal tissues was analyzed via UALCAN (TCGA), and the regulatory effects of rs9930506 and rs9940128 were assessed using GTEx data. A retrospective analysis was conducted on 870 CRC cases and 870 matched controls. Genotyping was performed using PCR-RFLP. Association with CRC risk was assessed by unconditional logistic regression with odds ratio ( OR ) and 95% confidence interval ( CI ), adjusted for age, sex, smoking status, and drinking status. Bioinformatics analysis revealed elevated FTO expression in colon cancer ( p = 0.043), but not in rectal cancer ( p = 0.250). Its variants rs9930506 and rs9940128 showed regulatory effects on gene expression in skeletal muscle and esophagogastric junction ( p < 0.001). The FTO variant rs9930506 A > G was significantly associated with reduced CRC risk across multiple genetic models (GG vs. AA: OR = 0.30, 95% CI = 0.16–0.56, p < 0.001; AG+GG vs. AA: OR = 0.76, 95% CI = 0.62–0.93, p = 0.007; GG vs. AG+AA: OR = 0.32, 95% CI = 0.17–0.59, p < 0.001). These protective associations were preserved in non-smokers (all p < 0.05) and non-drinkers (all p < 0.01). In contrast, rs9940128 showed no significant association with CRC risk in any genetic model or stratum (all p > 0.05). The FTO rs9930506 polymorphism is associated with reduced CRC risk in this population, suggesting its role as a potential susceptibility marker.