Journal Article

Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population

Boujelebene, Nadia, Mezlini, Amel, Zidi, Nour, Dziri, Olfa, Babay, Wafa, Laaribi, Ahmed Baligh, Sebai, Refaat, Chelbi, Hanene, Rifi, Hela, Zidi, Inès, Ben Yahia, Hamza, Ben Hassine, Amna

2016

Overview

HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C>G polymorphisms. The mutations were identified with PCR and PCR–RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C>G polymorphism ( p  = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008–0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C>G polymorphism is maintained in young patients (<50 years, p  = 0.0006) and in early-diagnosed BC patients (<50 years, p  = 0.0033). In addition, an association was found between the haplotypes inferred by both HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081–0.895, p  = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL ( p  < 0.0001). We demonstrated also that sHLA-G is closely associated with advanced stages of BC without significance. sHLA-G is increased in TNM IV and SBR III subgroups. It is also enhanced in patients with a tumor size over 20 mm and in triple-negative patients. Taken together, our findings demonstrate, for the first time, the association of HLA-G +3142 C>G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.

• Publisher: Springer US,Springer Nature B.V,Humana Press
• Subject: Adult / Age Factors / Aged / Allergology / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Carcinogenesis / Female / Gene expression / Gene Frequency / Genetic Association Studies / Genetic Predisposition to Disease / Genotype / Genotype & phenotype / HLA-G Antigens - genetics / Humans / Immunology / Internal Medicine / Life Sciences / Medicine/Public Health / Middle Aged / Neoplasm Staging / Original Article / Polymorphism / Polymorphism, Genetic / Population genetics / Risk / Sequence Deletion - genetics / Tunisia