Interaction Between Retinol Intake and ISX rs5755368 Polymorphism in Colorectal Cancer Risk: A Case-control Study Among the Korean Population
Abstract There is limited evidence about the interaction between retinol intake and the intestine-specific homeobox (ISX) rs5755368 polymorphism in colorectal cancer (CRC) risk. We conducted a hospital-based case-control study to examine whether the ISX rs5755368 genotypes are associated with the effect of dietary retinol consumption on CRC risk. First, to identify the association between dietary retinol and CRC risk, we recruited 923 CRC patients and 1846 controls. Dietary retinol intake was assessed using a semiquantitative food frequency questionnaire. For genetic analysis, genotype data were available for 1419 patients (600 cases and 819 controls) out of the total study population. ISX rs5755368 genotyping was performed using an Illumina MEGA-Expanded Array. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression models. Retinol intake was inversely associated with the development of CRC (OR = 0.49; 95% CI = 0.37–0.63) after adjusting for confounders. Patients with homozygous AA genotype of the ISX rs5755368 polymorphism were less likely to have CRC risk than subjects carrying the G allele (AG+GG) (OR = 0.76; 95% CI = 0.58–0.99). Additionally, a 68% reduced risk of CRC was related to the highest retinol intake among those carrying the rs5755368 AA genotype compared to the risk of participants carrying the G allele consumed the lowest retinol intake (OR = 0.32; 95% CI = 0.20–0.53; P interaction=0.026). In conclusion, our study confirmed a protective role of retinol intake in CRC risk reduction. Moreover, this association was strengthened significantly among individuals carrying the homozygous AA genotype of the ISX rs5755368 polymorphism.