Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs

Susceptibility and prognostic implications in Tunisians

Jingxuan Shan, Wijden Mahfoudh, Shoba P. Dsouza, Elham Hassen, Noureddine Bouaouina, Sonia Abdelhak, Ahlem Benhadjayed, Hager Memmi, Rebecca A. Mathew, Idil I. Aigha, Sallouha Gabbouj, Yassmine Remadi, Lotfi Chouchane

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)715-724
Number of pages10
JournalBreast Cancer Research and Treatment
Volume135
Issue number3
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Genome-Wide Association Study
Breast Neoplasms
Alleles
Genotype
Genes
Neoplasm Metastasis
Genetic Markers
Population
Single Nucleotide Polymorphism
Neoplasms
Healthy Volunteers
Lymph Nodes

Keywords

  • Arabs
  • Breast cancer
  • GWAS
  • Prognosis
  • Survival
  • Tunisians

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs : Susceptibility and prognostic implications in Tunisians. / Shan, Jingxuan; Mahfoudh, Wijden; Dsouza, Shoba P.; Hassen, Elham; Bouaouina, Noureddine; Abdelhak, Sonia; Benhadjayed, Ahlem; Memmi, Hager; Mathew, Rebecca A.; Aigha, Idil I.; Gabbouj, Sallouha; Remadi, Yassmine; Chouchane, Lotfi.

In: Breast Cancer Research and Treatment, Vol. 135, No. 3, 10.2012, p. 715-724.

Research output: Contribution to journalArticle

Shan, J, Mahfoudh, W, Dsouza, SP, Hassen, E, Bouaouina, N, Abdelhak, S, Benhadjayed, A, Memmi, H, Mathew, RA, Aigha, II, Gabbouj, S, Remadi, Y & Chouchane, L 2012, 'Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: Susceptibility and prognostic implications in Tunisians', Breast Cancer Research and Treatment, vol. 135, no. 3, pp. 715-724. https://doi.org/10.1007/s10549-012-2202-6
Shan, Jingxuan ; Mahfoudh, Wijden ; Dsouza, Shoba P. ; Hassen, Elham ; Bouaouina, Noureddine ; Abdelhak, Sonia ; Benhadjayed, Ahlem ; Memmi, Hager ; Mathew, Rebecca A. ; Aigha, Idil I. ; Gabbouj, Sallouha ; Remadi, Yassmine ; Chouchane, Lotfi. / Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs : Susceptibility and prognostic implications in Tunisians. In: Breast Cancer Research and Treatment. 2012 ; Vol. 135, No. 3. pp. 715-724.
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TY - JOUR

T1 - Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs

T2 - Susceptibility and prognostic implications in Tunisians

AU - Shan, Jingxuan

AU - Mahfoudh, Wijden

AU - Dsouza, Shoba P.

AU - Hassen, Elham

AU - Bouaouina, Noureddine

AU - Abdelhak, Sonia

AU - Benhadjayed, Ahlem

AU - Memmi, Hager

AU - Mathew, Rebecca A.

AU - Aigha, Idil I.

AU - Gabbouj, Sallouha

AU - Remadi, Yassmine

AU - Chouchane, Lotfi

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N2 - 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 breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population. In a cohort of 640 unrelated patients with breast cancer and 371 healthy control subjects, we characterized the variation of 9 single nucleotide polymorphisms (SNPs), namely rs1219648, rs2981582; rs8051542, rs12443621, and rs3803662; rs889312; rs3817198; rs13387042 and rs13281615. Only 5 out of 9 GWAS breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (G vs. A allele: OR = 1.36, P = 1 × 10 -3) and rs2981582 (A vs. G allele: OR = 1.55, P = 3 × 10 -6) of FGFR2 gene; the rs8051542 of the TNRC9 gene (T vs. C allele: OR = 1.40, P = 4 × 10-4); the rs889312 of the MAP3K1 gene (C vs. A allele: OR = 1.33, P = 3 × 10-3) and the rs13281615 located on 8q24 (G vs. A allele: OR = 1.21, P = 0.03). Homozygous variant genotypes of rs2981582 were strongly related to lymph node negative breast cancer (OR = 3.33, P = 6 × 10-7) and the minor allele of rs2981582 was associated with increased risk of ER+ tumors (OR = 1.57, P = 0.02; OR = 2.15, P = 0.001, for heterozygous and homozygous variant genotypes, respectively) and increased risk of distant metastasis development (OR = 2.30, P = 4 × 10-3; OR = 3.57, P = 6 × 10-5, for heterozygous and homozygous variant genotypes, respectively) in a dose dependent manner. The association for rs8051542 was stronger for high-grade SBR tumors (OR = 2.54, P = 2 × 10-4). GG genotype of rs13387042 on 2q35 showed a significant association with the risk of developing distant metastasis (OR = 1.94, P = 0.02). The G allele of rs1219648 in FGFR2 and the A allele of rs13387042 on 2q35 indicated a better prognosis by showing a significantly higher overall survival rates (P = 0.013 and P = 0.005, respectively). In conclusion, GWAS breast cancer FGFR2, TNRC9, MAP3K1, and 8q24 loci are associated with an increased risk of breast cancer and genetic variation in FGFR2 gene may predict the aggressiveness of breast cancer in Tunisians.

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

KW - Arabs

KW - Breast cancer

KW - GWAS

KW - Prognosis

KW - Survival

KW - Tunisians

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