title: Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
abstract: BACKGROUND
  BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.
  
  
  METHODS
  Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.
  
  
  RESULTS
  The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.
  
  
  CONCLUSIONS
  There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.
  
  
  CONCLUSIONS
  Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy. paolo.peterlongo@ifom.eu eitan.friedman@sheba.health.gov.il feitan@post.tau.ac.il.
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mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055815:Young Adult