Study of Human Leukocyte Antigen-G gene 14-bp Ins/Del and Codon 93 (CAC/CAT) Polymorphisms Association with Breast Cancer Susceptibility

Abstract

Human leukocyte antigen-G is a non-classic human leukocyte antigen I molecule. This protein is expressed aberrantly in numerous forms of malignant diseases like glioblastoma multiforme, ovarian cancer, lymphoblastic and breast cancer. Human leukocyte antigen-G polymorphisms association with breast cancer has been extensively studied. One amongst the foremost studied variants was human leukocyte antigen-G 14-base pair insertion/deletion polymorphism. Nevertheless, results are contradictory or inconclusive. We aim to investigate two human leukocyte antigen-G polymorphisms, 14-base pair insertion/deletion 3’ untranslated region and for the first time and codon 93 (CAC/CAT) polymorphisms potentially associated with breast cancer risk in the Tunisian population. This study involved 151 breast cancer patients and 187 healthy controls. Genotyping of the human leukocyte antigen-G codon 93 (CAC/CAT) and 14-base pair insertion/deletion variants was performed respectively by amplification-refractory mutation system and polymerase chain reaction. The analysis of genotype and allele frequencies revealed that human leukocyte antigen-G 14-base pair insertion/deletion polymorphism was associated with breast cancer susceptibility in the Tunisian population (Odds ratio=0.53, 95 % confidence interval=0.33-0.85, p=0.0022) without correlation with clinical parameters. We also observed an association of the human leukocyte antigen-G codon 93 (CAC/CAT) polymorphisms with breast cancer. In terms of analysis of the combined 14-base pair insertion/deletion and codon 93 CT genotype, we detected that the CC insertion/insertion and CC insertion/deletion genotype decrease the risk of breast cancer development (Odds ratio=0.2083; p=0.0097; Odds ratio=0.3571; p=0.0053, respectively). In addition, the haplotype frequency distribution analysis disclosed that the C insertion haplotype has a protective effect against breast cancer development (Odds ratio=0.4749; 95 % confidence interval=0.4425-0.9277; p=0.0153). Taken together, female’s homozygosity for human leukocyte antigen-G 14-base pair insertion and human leukocyte antigen-G codon 93 (CAC) alleles may protect against breast cancer susceptibility.