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. <i>rs4784227-CASC16</i> and <i>rs4782447-ACSF3</i>, as single nucleotide polymorphisms (SNPs), located at the <i>16q</i> may affect the FOXA1 DNA binding sequence change and therefore may enhance the FOXA1-binding affinity to the promoter of <i>TOX3</i> gene. This study aimed to investigate the association of these SNPs/haplotypes with breast cancer susceptibility in an Iranian population. We conducted a case-control study of 1072 blood samples (505 breast cancer patients and 567 controls). Genotyping of <i>rs4784227-CASC16</i> and <i>rs4782447-ACSF3</i> SNPs was carried out by ARMS-PCR. Moreover, statistical analysis was done using SPSS version 20.0 (IBM Inc., Chicago, IL, USA), PHASE v 2.1 and SNP analyser 2.0. There was a strongly significant statistical association between alleles and genotypes of <i>rs4784227-CASC16</i> with breast cancer risk in our study population (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- <i>_value</i> =0.025). In this respect, although we did not observe a statistically significant association between <i>rs4782447-ACSF3</i> with breast cancer susceptibility, the combination of the effects of <i>rs4784227-CASC16</i> and <i>rs4782447-ACSF3</i> SNPs may also affect the risk. This is in line with other studies suggesting these SNPs as risk-associated polymorphisms which may lead to a change in the affinity of FOXA1, as a distal enhancer, to <i>TOX3</i> and thus change in <i>TOX3</i> expression, which can eventually affect the risk of breast cancer.