Association of MT1A rs11640851, rs8052394 and rs11076161 polymorphisms with the risk of developing breast cancer: a haplotype-based case-control study and in silico analysis

Abstract

Metallothionein 1A (MT1a) is involved in many pathological conditions associated with antioxidant defense and detoxification, including cancer. The aim of this study was to investigate the possible association of MT1A rs11640851, rs8052394, and rs11076161 single nucleotide polymorphisms (SNPs) with the risk of breast cancer (BC) and clinicopathological features. The study included 100 patients with BC and 100 healthy controls. We genotyped the MT1A SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system PCR (ARMS-PCR) techniques. The genotypic and allelic associations of MT1A SNPs with susceptibility to BC were assessed using logistic regression analysis under co-dominant, dominant, and recessive inheritance models. The combined effect of MT1A SNPs on the BC risk was determined using the haplotype analysis. In silico analysis was performed using the Polyphen-2 and RNAsnp online servers. The rs11640851 was found to be associated with a reduced risk of BC in all three inheritance models (P < 0.05). We also found that rs11640851 A allele has a protective effect against BC (OR: 4.812; 95% CI: 2.655–8.719; P < 0.0001). For rs8052394/rs11076161, carriers of AG/AA combined genotype had a 3.84-fold increased risk for developing BC. The haplotypes CAC and CGA were significantly associated with BC susceptibility. The rs11640851 was predicted to be deleterious using Polyphen-2 server. This study provides the first evidence that rs11640851 is significantly associated with a reduced risk of BC suggesting its protective role in the development of BC. Two haplotypes CAC and CGA were also identified as risk factors for BC.