HLA-DRB1 ALLELE POLYMORPHISMS IN GENETIC SUSCEPTIBILITY TO COLORECTAL CANCER

HLA Class II antigens are key mediators of the immune response and are expressed on dendritic cells and in subpopulations of macrophages. HLA Class II antigens professionally present exogenous antigens to CD4+ T cells. They are highly polymorphic, with the majority of the polymorphisms resulting from functional amino acid changes leading to a significant variability in individual antigens response. This variability may have particular significance in colon tissues, since its continuous exposure to food, chemicals and bacteria antigens may result in a constant state of controlled inflammation. HLA-DRB1 allele polymorphisms were typed by sequence-based typing (SBT) method in 39 colorectal patients including 36 CRC, 2 adenomas and 1 lipoma while 297 normal individuals were utilized as historical controls. Chi-squared analysis or Fisher's Exact test with Bonferroni's correction were used to compare the allele frequency (AF) of HLADRB1 between the patients and controls. In this case-control study, a total of 11 HLA-DRB1 alleles were identified; amongst these, DRB1*13 and DRB1*03 were significantly associated with increased risk of colorectal cancer. In particular, CRC-cases were more likely to have the DR13 alleles than controls. We identified three different DR13 alleles: DRB1*13:01, 13:02 and 13:03. AF of DRB1*13:01 was significantly higher in CRC patients than in normal controls (9% vs 2%; p = 0.001 Odds Ratio 4.78) even after correction (p = 0.03) used for multiple comparisons. No significant association with CRC was established for DRB1*13:02 and DRB1*13:03. With regard to DRB1*03, we found that DRB1*03:01 was present at increased frequency in CRC patients (10% vs 3.3%; p = 0.01 OR 3.23). There was no association between patients and controls in the remaining HLADRB1 alleles. This study suggests that HLA-DRB1*13:01 could be a potential marker for predicting genetic susceptibility of normal individuals to CRC. Therefore, it is necessary to verify these results in more patients.