Clinical implication of soluble hla-g and immunogenetic influence of hla-g +3142g/c polymorphism in breast cancer development among patients attending ORCI in Tanzania

Abstract

ABSTRACT Background: Breast cancer is among the most prevalent cancers in Tanzania. Cancer arises from aberration in regulatory systems controlling cell cycle. Many altered (tumor) cells are kept in check by the immune system due to their altered expression of cell surface molecules. Yet some tumor cells do manage to escape immune recognition and develop into malignancy, and immunosuppressive HLA-G is thought to be expressed more by tumor cells and enable them achieve this immune escape. Soluble Human Leukocyte Antigen-G (sHLA-G) has been closely associated with diagnosis and prognosis in many types of human cancer.Moreover, +3142G/C polymorphism (rs1063320) in HLA-G gene affects its expression, and G is considered to be a protective mutant allele associated with less expression of HLA-G. The implication of HLA-G in cancer development has been reported in different cancers and in different populations. But, its implication in Tanzanian population has not yet been investigated. Aim: The goal of this study was to investigate the extent of soluble HLA-G level and the frequencies distribution of +3142G/C genetic variants affecting its expression, and their associations with cancer development among breast cancer patients attending ORCI in Tanzania. Method: This was a case-control study, where 75 breast cancer patients and 84 normal healthy women were recruited. Most patients (81.3%) had undergone mastectomy and were under adjuvant therapy. The remaining patients, though non-mastectomized were also under treatment regimen. Plasma level of soluble HLA-G protein was determined by ELISA. The genotyping of HLA-G +3142G/C polymorphism was determined by LightSNiP typing assay using quantitative Real-Time PCR. Results: The frequencies distribution of +3142C/G genotypes and alleles were relatively similar between patients and controls (Genotype, p=0.537; Alleles, p=0.650). The protective genotype GG was weakly associated with breast cancer: OR=1.26 (CI 95% 0.6-2.65). The level of sHLA-G molecule in breast cancer patients was significantly lower than that in normal healthy women (p<0.001), with an area under the receiver operating characteristics (ROC) curve of 0.697 (CI 95%=0.619-0.767, p<0.001). No significant associations of sHLA-G level were found with respect to metastatic and receptors expression (ER, PR and HER2) status. However, sHLA-G level was significantly higher in non-mastectomized group compared to mastectomized one (p=0.017). Conclusion: The results show low levels of sHLA-G and poor association of +3142G/C SNP with breast cancer among Tanzanian breast cancer patients undertaking neoadjuvant and adjuvant therapies. Medical interventions are more likely to have lowered sHLA-G in these breast cancer patients. More studies with increased sample size including patients with early stage breast cancer and controlling medical interventions are recommended to reach a clear conclusion in order to provide evidence in further support of the application of sHLA-G as a biomarker for breast cancer diagnosis and monitoring of breast cancer therapy in Tanzania. Key words: Breast cancer, soluble HLA-G, +3142G/C HLA-G, Diagnosis, Mastectomy, Tanzania.