Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians

• DOI: 10.1007/s10549-012-2202-6
• Publication Date: 2012-08-21T06:38:19Z
• Authors: Jingxuan Shan; Wijden Mahfoudh; Shoba P. Dsouza; Elham Hassen; Noureddine Bouaouina; Sonia Abdelhak; Ahlem Benhadjayed; Hager Memmi; Rebecca Ann Mathew; Idil I. Aigha; Sallouha Gabbouj; Yassmine Remadi; Lotfi Chouchane
• Keywords: Genome-wide Association Study; Genetic Association

Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with in Arab Population. Therefore, we designed a broad study to investigate susceptibility prognostic implications of GWAS loci Tunisian population. In cohort 640 unrelated patients 371 healthy control subjects, characterized variation 9 single nucleotide polymorphisms (SNPs), namely rs1219648, rs2981582; rs8051542, rs12443621, rs3803662; rs889312; rs3817198; rs13387042 rs13281615. Only 5 out were found be significantly Tunisians: The rs1219648 (G vs. A allele: OR = 1.36, P 1 × 10(-3)) rs2981582 (A G 1.55, 3 10(-6)) FGFR2 gene; rs8051542 TNRC9 gene (T C 1.40, 4 10(-4)); rs889312 MAP3K1 (C 1.33, rs13281615 located on 8q24 1.21, 0.03). Homozygous variant genotypes strongly related lymph node negative (OR 3.33, 6 10(-7)) minor allele was increased ER+ tumors 1.57, 0.02; 2.15, 0.001, heterozygous homozygous genotypes, respectively) distant metastasis development 2.30, 10(-3); 3.57, 10(-5), dose dependent manner. association stronger high-grade SBR 2.54, 2 10(-4)). GG genotype 2q35 showed significant developing 1.94, 0.02). indicated better prognosis by showing higher overall survival rates (P 0.013 0.005, respectively). conclusion, FGFR2, TNRC9, MAP3K1, are an may predict aggressiveness Tunisians.