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

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.

Pregnancy and breastfeeding: a new theory for sHLA-G in breast cancer patients?

It is now widely recognized that HLA-G molecule is implicated in immune tolerance and particularly in immune subversion of tumor cells. In this study, we explored levels of soluble HLA-G (sHLA-G) in plasma samples obtained from women with breast cancer (BC). Additionally, we correlated sHLA-G concentration with pregnancy and breastfeeding history. We reported in this preliminary work significant differences in sHLA-G levels between BC patients with/without breastfeeding experience (p = 0.04). Interestingly, among women with BC, only those without previous pregnancy experience present significant increase in sHLA-G (p = 0.02). Of relevance, we demonstrated that patients without both pregnancy and breastfeeding history have advanced SBR III grade, associated with significant enhancement in tumor size compared with patients who had both experiences (p = 0.028). Taken together, our results indicate the potential implication of previous pregnancy and breastfeeding experience in sHLA-G expression during BC. We theorized that having pregnancy and breastfeeding history may protect against advanced BC stages.