title: Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis.
abstract: Genetic variation in SIPA1, signal-induced proliferation-associated gene 1, has been proposed to be associated with aggressive breast tumor characteristics related to metastasis and worse prognosis in humans and rodents. To test this hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at -3092 (A<G, rs931127), exon 3-135 (C>T, rs3741378), and exon 14 + 14 (C>T, rs746429), and examined them in relation to breast cancer risk and overall survival, stratified by tumor characteristics in 2 independent case-control studies conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases, 2,257 controls). Vital status (n = 396 deaths) was available for 911 Polish and 1,919 British breast cancer cases with an average follow-up time of 5.5 years. Overall, we found no significant associations between genetic variants of SIPA1 SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals (CI): rs931127-0.99, 0.93-1.06; rs3741378-1.03, 0.94-1.13; and, rs74642-0.98, 0.92-1.04). In both studies, SIPA1 polymorphisms were not related to overall mortality (per allele hazard ratios, 95% CI: 1.02, 0.88-1.17; 0.90, 0.72-1.11; 1.04, 0.90-1.21, respectively). Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. gaudetm@mskcc.org
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Kent
authors.initials: K
authors.lastname: Hunter
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Kristy
authors.initials: K
authors.lastname: Driver
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Mark
authors.initials: M
authors.lastname: Sherman
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors
chemical_list: D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human