Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast and/or ovarian cancer patients.
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.
Rao
Nan-Yan
NY
Department of Oncology, Breast Cancer Institute, Cancer Hospital, Shanghai Medical College, Fudan University, Shanghai, PR China.
Hu
Zhen
Z
Li
Wen-Feng
WF
Huang
Juan
J
Ma
Zhong-Liang
ZL
Zhang
Bin
B
Su
Feng-Xi
FX
Zhou
Jie
J
Di
Gen-Hong
GH
Shen
Kun-Wei
KW
Wu
Jiong
J
Lu
Jin-Song
JS
Luo
Jian-Min
JM
Yuan
Wen-Tao
WT
Shen
Zhen-Zhou
ZZ
Huang
Wei
W
Shao
Zhi-Ming
ZM
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*