Association between HLA-G 3' UTR 14-bp ins/del polymorphism and susceptibility to breast cancer

Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that is highly expressed in cancer pathologies. A 14-bp insertion/deletion polymorphism in exon 8 of the 3' untranslated region (3'-UTR) of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. This study aimed to evaluate the association of 14-bp ins/del polymorphism in HLA-G gene and breast cancer in a south-east Iranian population. This study was performed using 236 patients with breast cancer and 203 healthy subjects. We designed a rapid and simple bi-directional PCR allele-specific amplification (Bi-PASA) for detection of 14-bp ins/del polymorphism in the HLA-G gene. The results of our study revealed that the prevalence of HLA-G 14-bp homozygote deletion genotype was higher in breast cancer patients than in the control group (OR = 2.06, 95% CI = 1.23-3.44, P = 0.006). The frequency of the Del allele was 56.4% in breast cancer patients and 46.5% in the control group and the difference was statistically significant (OR = 1.48, 95% CI = 1.13-1.94, P = 0.004). Moreover we evaluated the possible correlation of the HLA-G 14-bp ins/del genotypes and clinical characteristics of the patients, but no statistically significant correlation was found (P > 0.05). Our findings, for the first time, suggest that the 14-bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma. Further studies on larger populations with different ethnicities are required to verify our findings.