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

Autor: Idil I. Aigha, Hager Memmi, Lotfi Chouchane, Wijden Mahfoudh, Noureddine Bouaouina, Jingxuan Shan, Sonia Abdelhak, Sallouha Gabbouj, Elham Hassen, Rebecca Mathew, Ahlem Benhadjayed, Yassmine Remadi, Shoba P Dsouza
Přispěvatelé: Laboratory of Genetic Medicine & Immunology, Weill Cornell Medicine [Qatar], Laboratory of Molecular Immuno-oncology, Faculté de Médecine de Monastir [Tunisie], Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This publication was made possible by a grant from the Qatar National Research Fund (NPRP08-083-3-031). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Qatar National Research Fund. This work was also supported by the Ministry of Higher Education and Scientific Research and the Ministry of Public Health of the Republic of Tunisia.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Cancer Research
Survival
[SDV]Life Sciences [q-bio]
Genome-wide association study
0302 clinical medicine
Preclinical Study
Breast cancer
MESH: Aged
80 and over
Genotype
GWAS
MESH: Heterozygote
Genetics
Aged
80 and over
MESH: Aged
0303 health sciences
MESH: Middle Aged
MESH: Polymorphism
Single Nucleotide
High Mobility Group Proteins
MESH: Genetic Predisposition to Disease
Middle Aged
Prognosis
MESH: Case-Control Studies
3. Good health
Arabs
Receptors
Estrogen
Oncology
030220 oncology & carcinogenesis
Chromosomes
Human
Pair 2
MESH: Receptors
Estrogen
Female
Tunisians
Receptors
Progesterone
MESH: Tunisia
Chromosomes
Human
Pair 8
Adult
MESH: Receptors
Progesterone
Heterozygote
Tunisia
MESH: Receptor
Fibroblast Growth Factor
Type 2
MESH: Chromosomes
Human
Pair 2
MAP Kinase Kinase Kinase 1
Single-nucleotide polymorphism
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
Genetic variation
medicine
Humans
Genetic Predisposition to Disease
Allele
Receptor
Fibroblast Growth Factor
Type 2
030304 developmental biology
Genetic association
Aged
MESH: MAP Kinase Kinase Kinase 1
MESH: Humans
MESH: Adult
medicine.disease
Minor allele frequency
Case-Control Studies
MESH: Genome-Wide Association Study
Trans-Activators
MESH: Arabs
Apoptosis Regulatory Proteins
MESH: Chromosomes
Human
Pair 8
MESH: Female
MESH: Breast Neoplasms
Genome-Wide Association Study
Zdroj: Breast Cancer Research and Treatment
Breast Cancer Research and Treatment, Springer Verlag, 2012, 135 (3), pp.715-24. ⟨10.1007/s10549-012-2202-6⟩
ISSN: 0167-6806
1573-7217
DOI: 10.1007/s10549-012-2202-6⟩
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s10549-012-2202-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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