An Analysis of IL-10/IL-10R Genetic Factors Related to Risk of Colon Cancer and Inflammatory Bowel Disease in a Han Chinese Population.

Abstract

Patients with chronic inflammatory bowel disease (IBD) are at high risk of developing colon cancer and represent a valuable patient cohort for studying the correlation between chronic inflammation and cancer formation. Cytokines play key roles in the regulation of systemic inflammation, local tissue damage, and immunomodulation involved in tumor development and progression. Therefore, functional polymorphisms in genes that encode cytokines and cytokine receptors represent potential candidate genes associated with carcinogenesis. The present study aimed to ascertain if any of the candidate single nucleotide polymorphisms (SNPs) in inflammation-related genes IL-10/IL-10R are associated with colon cancer or IBD in Han Chinese population. A case-control study in a Chinese Han cohort was conducted and included 375 patients with colon cancer, 278 patients with IBD, and 382 age and gender matched healthy controls. Genotyping of four candidate SNPs (IL-10 rs1800896, rs1800872, rs3024505, and IL-10R rs9610) was performed and analysis was done using the MassARRAY system based on the MALDI-TOF MS platform. The C allele at rs1800872 may be a protective factor incolon cancer (OR = 0.770; 95% CI: 0.653 - 0.909; p = 0.002). A decreased risk of colon cancer in patients with rs1800872 AC genotype (OR = 0.794; 95% CI, 0.664 - 950; p = 0.011), CC genotype (OR = 0.589; 95% CI, 0.372 - 0.933; p = 0.022) or AC/CC genotype (OR = 792; 95% CI, 0.678 - 0.925; p = 0.003) was observed, compared with the common AA genotype. Conversely, carriers of the variant T allele of rs3024505 flanking the IL-10 gene were at increased risk of IBD (OR = 1.999; 95% CI: 1.174 - 3.401; p = 0.009). Compared with the common CC genotype, carrying heterozygous (OR = 1.762; 95% CI, 1.030 - 3.012; p = 0.036), or heterozygous and homozygous combined (OR = 1.874; 95% CI, 1.105 - 3.177; p = 0.018) at the IL-10 rs3024505, was associated with increased risk of IBD. Stratified analysis showed that a positive association was identified between the AC/CC genotype at IL-10 rs1800872 and tumor stage (p = 0.029). These data suggest that the variants in the IL-10 gene may change the risk of both colon cancer and IBD. The C allele at rs1800872 may be a protective factor in colon cancer and the T allele at rs3024505 may be a risk factor in IBD in a Han Chinese population.