Hla-Drb1*13:01 Allele In The Genetic Susceptibility To Colorectal Carcinoma

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p=0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p=0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.What's new? Altered expression of the HLA-DRB1 antigen, a key player in the immune response, is linked to colorectal cancer with a background of ulcerative colitis. But it is unknown whether HLA-DRB1 alleles affect risk of colorectal tumor development, and their impact in the absence of inflammatory bowel disease remains relatively unexplored. In this study, 29 distinct HLA-DRB1 alleles were identified in colorectal cancer patients and normal controls. One allele, DRB1*13:01, was found to be significantly associated with increased risk of colorectal tumor, suggesting that it may be a marker for colorectal cancer outside the setting of inflammatory bowel disease.