title: Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast and/or ovarian cancer patients.
abstract: OBJECTIVE
  Our aim was to find an appropriate method to estimate the likelihood that a family history of cancer was a result of a mutation in the BRCA1 or BRCA2 genes. We also compared the performance of the established method with three different methods (Couch, Sh-E and BRCApro) to identify an alternative strategy for genetic council targeted to the specified population.
  
  
  METHODS
  The family history as well as individual information of two hundred unrelated probands who had completed BRCA1 and BRCA2 mutation screening was analyzed to assess the likelihood of a pathogenic mutation. A model was developed by empirical method. The performance of this model was validated in a separate patient cohort compared with BRCApro.
  
  
  RESULTS
  Several factors were associated with mutations in univariate analysis and a logistic model was devised to estimate the probability for a proband of harboring a mutation in BRCA1 and/or BRCA2. Using a greater than 10% probability threshold, the highest accuracy was achieved by the established model when compared to other three models, presenting the highest sensitivity, PPV, NPV and area under ROC curve. The empirical model showed a better ROC curve compared to BRCApro in the verification cohort.
  
  
  CONCLUSIONS
  A probability model targeted to Han Chinese population should be a useful tool in the genetic counseling for the specified ethnic. Its ability to predict BRCA2 mutation carriers needs to be improved.
authors.affiliation: Department of Oncology, Breast Cancer Institute, Cancer Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Nan-Yan
authors.initials: NY
authors.lastname: Rao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Feng-Xi
authors.initials: FX
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Gen-Hong
authors.initials: GH
authors.lastname: Di
authors.forename: Kun-Wei
authors.initials: KW
authors.lastname: Shen
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Lu
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Luo
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Yuan
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*