Background Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin ( GHRL), resistin ( RETN) and insulin receptor substrate 1 ( IRS1) were associated with CRC risk. Methods This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method. Results No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively). Conclusions In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.
Gly972Arg Variant of Insulin Receptor Substrate 1 Gene and Colorectal Cancer Risk in Overweight/Obese Subjects
