title: Breast cancer susceptibility alleles and ovarian cancer risk in 2 study populations.
abstract: Recent genome-wide scans identified several novel breast cancer risk alleles, including variants of the FGFR2, MAP3K1 and LSP1 genes, and a study of associations between these alleles and characteristics of breast cancer patients reported a borderline significant correlation between the number of FGFR2 minor alleles and family history of breast/ovarian cancer. Given these results and similarities in the etiology of breast and ovarian cancer, we examined the association between 7 novel breast cancer susceptibility alleles and epithelial ovarian cancer risk in 2 large study populations. Our analysis included 1,173 cases and 1,201 controls from a New England-based Case-Control study and 210 cases and 603 controls from the prospective Nurses' Health Study. We used logistic regression to estimate the odds ratio (OR) for individuals heterozygous or homozygous for the minor allele at each locus, compared to individuals with the wild-type genotype. We examined the associations separately in each population and, after testing for heterogeneity in the results, pooled the estimates using a random effects model. There was no clear association between these polymorphisms and ovarian cancer risk in either population. The pooled per allele OR for FGFR2 was 1.06 (95% confidence interval (CI)=0.95-1.18) for rs1219648 and 1.04 (95% CI=0.93-1.15) for rs2981582. We had more than 80% power to detect a log-additive OR of 1.16-1.18 per allele at the alpha=0.05 level in the pooled analysis. Our results do not provide strong support for an association between these breast cancer susceptibility alleles and epithelial ovarian cancer risk.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. nhmag@channing.harvard.edu
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Gates
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics
chemical_list: C489183:LSP1 protein, human; D008840:Microfilament Proteins; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human