Abstract:

Objective

To investigate the prevalence of BRCA (breast cancer susceptibility gene)1/2 gene mutations among familial and sporadic breast cancer patients in Hebei Province of China.

Methods

The BRCA1/2 gene mutation and genomic DNAs from peripheral blood cells of 18 familial breast cancer patients,50 sporadic breast cancer patients,23 breast benign tumor patients and 20 health controls were studied using polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing.Chi-square test or Fisher's exact propability test was used for analysis of qualitative data,and Student's t test was used for analysis of quantitative data.

Results

The incidence of gene mutation in breast cancer patients was 7.35% (5/68).All of these mutations (162ATT ＞TTT,4142GTT＞GTG,4196CAA＞CAT,4196del A,4142GTT＞GTG,5379GAA＞AAA)were localized in BRCA1 instead of BRCA2.The mutation rate of BRCA1 was much higher than that of BRCA2(χ²=4.829,P=0.028).Of the 68 breast cancer patients,the BRCA1 mutation rate of familial breast cancer(16.67%,3/18)was higher than that of sporadic breast cancer(4.00%,2/50),but there was no significant difference(χ²=3.117,P=0.111).No BRCA1/2 mutation was found in the breast benign tumor patients.No BRCA1 mutation but a BRCA2 mutation (TTTCAGA ＞TGTCAA (6291insG,6294delG))was found in the health controls.There was a statistical difference in the BRCA1 mutation rate among the familial breast cancer patients,the sporadic breast cancer patients,the breast benign tumor patients and the health controls(χ²=8.248,P=0.041).In addition,a mononucleotide polymorphism at the 35th base downstream from BRCA1 exon 20 G＞A (IVS20+35G＞A)was found in one of the familial breast cancer patients.

Conclusions

Our data has enriched the information of mutation spectrum of BRCA1/2 gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.

Key words: Polymerase chain reaction-single strand conformation polymorphism analysis, Gene sequencing, BRCA1/2, Mutation, Breast Neoplasms