Association of HLA-G 3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

Aim Human leucocyte antigen-G (HLA-G) and tumour necrosis factor-alpha (TNF-alpha) are potent immune mediators implicated in the pathogenesis of breast cancer. The polymorphisms in the 3' untranslated region (3'UTR) of HLA-G and promoter region of TNF-alpha are well known to influence their expression levels and may consequently contribute to varied disease predisposition. Therefore, in the present study, we explored the effect of HLA-G 3'UTR (14-bp Ins/Del and +3142C/G) and TNF-alpha promoter (-238 G/A and -308 G/A) polymorphisms on breast cancer risk among South Indian women. Methods A total of 342 women (100 patients with breast cancer, 142 patients with benign breast disorder and 100 healthy women volunteers) were enrolled for this study. Genotyping of HLA-G and TNF-alpha polymorphisms were performed by direct PCR DNA amplification and amplification refractory mutation system PCR methods, respectively. Results Significantly higher frequencies of HLA-G 14-bp Ins allele and Ins/+3142G haplotype were observed in patients with breast cancer than healthy controls (OR=1.56, P-c=0.036) and patients with benign breast disorder (OR=1.47, P-c=0.046). Similarly, subgroup analysis based on age at diagnosis (age <= 50 years and >50 years) of breast cancer revealed higher frequencies of 14-bp Ins allele and Ins/+3142G haplotype in the patients of age >50 years than healthy controls (OR=1.77, P-c=0.03). Additionally, the extended haplotypes and multifactor dimensionality reduction analysis of the studied polymorphisms revealed significant contribution of HLA-G 14-bp Ins/Del polymorphism towards breast cancer risk. Conclusion The findings of the present study suggest that the HLA-G 14-bp Ins/Del polymorphism could influence breast cancer pathogenesis among South Indian women.