P1.07 New Genetic Variants ARE Associated with Breast Cancer Susceptibility & Aggressiveness in the Tunisian Population

Abstract

ABSTRACT Introduction Most late-onset cases occur in the absence of a first-degree family history of breast cancer and are often called “sporadic”cases. Single nucleotide polymorphisms (SNPs) may be causally related to breast cancer risk or be indirectly associated with breast cancer risk through linkage disequilibrium with a causal sequence variant. Risk-associated SNPs will have different frequencies among women with or without breast cancer and can be detected using genetic association studies. Recently, several genome-wide association studies (GWAS) have identified novel risk alleles for breast cancer including those related to FGFR2, TNRC9, MAP3K1, LSP1 genes and other locus. Replication in independent population samples is essential for validation of the results of any genome-wide association. Since SNPs are common, they are likely to be shared across different populations with diverse ancestries. It would be of interest to determine and investigate the potential implications of these novel markers revealed by GWAS to predict the “sporadic”breast cancer risk and progression in MENA populations. Materials and Methods Using TaqMan® SNP Genotyping Assays, we characterize 9 SNPs (include rs1219648, rs2981582, rs8051542, rs12443621, rs3803662, rs889312, rs3817198, rs13387042 and rs13281615) for 520 patients with sporadic breast cancer and 360 healthy controls in the Tunisian population. The association between the genotypes and breast cancer susceptibility and tumors characteristics was estimated by computing odds ratio (OR) and 95% confidence levels from logistic regression analyses. Association of the genetic marker with the rates of breast cancer overall survival was assessed using univariate analysis. Results Four out of nine GWAS-breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (OR = 1.23, P = 0.002) and rs2981582 (OR = 1.33, P = 0.003) SNP of FGFR2 gene; the rs8051542 of the TNRC9 gene (OR = 1.43, P = 0.0003) and the rs889312 of the MAP3K1 gene (OR = 1.33, P = 0.006). The FGFR2 G-rs2981582 allele showed a significant association with risk of lymph node metastasis and reduced overall survival rate. Conclusions Our results for the first time replicated the results of breast cancer GWAS in the Arabic population and indicated that some polymorphisms are associated with increased breast cancer risk and disease progress in the Tunisian population.