Association of genetic variant (rs4784227) at TOX3 gene with the risk of breast cancer in Iranian population

Breast cancer is one of the most common malignancies, ranking first in incidence and second in mortality for all cancers diagnosed among women in worldwide. Genetic factors play an important role in the etiology of breast cancer.TOX3, a gene of uncertain function containing a tri-nucleotide repeat motif, encodes aputative high-mobility-group (HMG) box motif nuclear protein, suggesting that it might act as atranscription factor that may be involved in calcium-dependent transcription. Its protein expression has been suggested to predict breast cancer metastasis to bone. Recent studies has provided strong in vitro evidence implicating TOX3 rs4784227 as a functional variant for breast cancers in Asian women. SNP rs4784227 is located 18.4 kb upstream of the TOX3 gene and in the evolutionarily-conserved region of intron of the LOC643714 gene. Although in European Americans rs4784227 is in strong linkage disequilibrium ( LD ) with one of the previously-reported SNPs, rs3803602, the positive association of rs4784227 with breast cancer remained after adjusting for previously-reported SNPs. In vitro experiments showed that risk allele T reduced luciferase activity and altered DNA-protein binding patterns. These results implicate rs4784227 as a functional genetic risk variant for breast cancer, and this SNP may explain, at least partially, the association of breast cancer with other SNPs identified in 16q12.1.Jirong Long et al. identified SNP rs4784227 as highly significantly associated with breast cancer in both Asians (per allele OR= 1.25, 95% CI = 1.20–1.31, P = 3.2610225) and European Americans (per allele OR= 1.19, 95% CI =1.09–1.31, P =1.361024). SNP rs4784227 is located at 16q12.1, a region reported previously to harbor breast cancer genetic risk variants among European descendents.In this breast cancer case–control study of Persian women, we investigate the associations of one candidate SNP of TOX3 ( rs4784227 ) and risk of sporadic breast cancer in IRAN.We will genotype one polymorphism ( rs4784227 with the risk T allele ) of the TOX3 gene using TETRA ARMS-PCR to determine whether previously identified breast cancer susceptibility allele are associate with sporadic breast cancer in the Iranian population.

کلیدواژه ها:

Breast cancer ، TOX3 ، 16q12.1 ، SNP