Impact of Chondroitin Sulfate Proteoglycan 4 Pseudogene 12 Genetic Variants on Colorectal Cancer Risk: A Case-Control Study.

Abstract

This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of CSPG4P12 (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of CSPG4P12 single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The CSPG4P12 exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: p = 0.006; CA + AA vs. CC: p = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: p = 0.024; CA + AA vs. CC: p = 0.014) and younger individuals (CA vs. CC: p = 0.004; CA + AA vs. CC: p = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001) and nondrinkers (CA vs. CC: p = 0.002; CA + AA vs. CC: p = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: p = 0.016; CA + AA vs. CC: p = 0.036) and nondrinkers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Haplotype analysis showed that the CSPG4P12 T_rs2880765C_rs6496932G_rs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (CSPG4P12 A_rs2880765C_rs6496932C_rs8040855) (OR = 0.46, 95% CI = 0.26-0.82, p = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.