Association of rs4784227-CASC16 (LOC643714 locus) and rs4782447-ACSF3 polymorphisms and their association with breast cancer risk among Iranian population

Abstract

TOX3 and FOXA1 proteins are believed to be involved in the susceptibility of breast cancer. rs4782447 and rs4784227, as single nucleotide polymorphisms (SNPs), located at the 16q may affect the FOXA1 DNA binding sequence change and therefore may enhance the FOXA1-binding affinity to the promoter of TOX3 gene. This study aimed to investigate the association of these SNPs/haplotypes with breast cancer susceptibility in Iranian population. We conducted a case-control study of 1072 blood samples (505 breast cancer patients and 567 controls). Genotyping of rs4784227 and rs4782447 SNPs was carried out by ARMS PCR. Moreover, statistical analysis was done by SPSS 20.0 (IBM Inc., Chicago, IL, USA) and SNP analyser 2.0. There was a strongly significant statistical association between alleles and genotypes of rs4784227 with breast cancer susceptibility in a group of Iranian women (p<0.05). Moreover, a significant association was demonstrated between TA haplotype and breast cancer risk (OR=0.78; 95% CI (0.62-0.96); P-value=0.025). In this respect, although we did not observe a statistically significant association between rs4782447 with breast cancer susceptibility, the combination of the alleles of rs4784227 and rs4782447 SNPs may also affect the risk. This is in line with other studies where they suggest these SNPs as risk-associated polymorphisms by which lead to disruption of as a distal enhancer, FOXA1, binding and following that change in TOX3 expression that can eventually affect the risk of breast cancer.