title: FGFR2 is a breast cancer susceptibility gene in Jewish and Arab Israeli populations.
abstract: Genetic variation in FGFR2 is a newly described risk factor for breast cancer. We estimated the relative risk and contribution of FGFR2 polymorphisms to breast cancer risk in diverse ethnic groups within Jewish and other Middle Eastern populations. We genotyped four FGFR2 single nucleotide polymorphisms (SNP) and tested for association of these SNPs and haplotypes with breast cancer risk in a population-based case-control study of 1,529 women with breast cancer and 1,528 controls. We found significant associations between breast cancer risk and all four studied SNPs in FGFR2 (P trend for all SNPs < 0.0001). In ethnicity-specific analysis, all four SNPs were significantly associated with breast cancer risk in Ashkenazi and Sephardi Jews, with a similar but not significant trend in Arabs. Haplotype analysis identified five common haplotypes (>1%). The previously described AAGT risk haplotype was significantly associated with breast cancer risk in Ashkenazi [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 1.07-1.45; P = 0.0059] and Sephardi Jews (OR, 1.46; 95% CI, 1.17-1.80; P = 0.0006) compared with the reference GGAC haplotype. The AAAC haplotype was significantly associated with breast cancer risk in Sephardi Jews (OR, 1.97; 95% CI, 1.16-3.35; P = 0.0125) but not in Ashkenazi Jews (OR, 0.83; 95% CI, 0.41-1.62; P = 0.5613) or in Arabs (OR, 1.31; 95% CI, 0.80-2.14; P = 0.2881). Genetic variation in FGFR2, identified by rs1219648, may account for a substantial fraction of breast cancer in Arab (12%), Ashkenazi (15%), and Sephardi Jewish (22%) populations. The identification of population-specific risk haplotypes in FGFR2 is likely to help identify causal variants for breast cancer.
authors.affiliation: Department of of Internal Medicine, University of Michigan Medical School and School of Public Health, Ann Arbor, MI 48109, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Raskin
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Chana
authors.initials: C
authors.lastname: Arad
authors.forename: Flavio
authors.initials: F
authors.lastname: Lejbkowicz
authors.forename: Ada
authors.initials: A
authors.lastname: Tamir
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D018912:Arabs / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
chemical_list: C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2