The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified.
To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP-DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (P = 0.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (P < 0.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese.
Li
Wen-Feng
WF
Department of Oncology, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, PR China.
Hu
Zhen
Z
Rao
Nan-Yan
NY
Song
Chuang-Gui
CG
Zhang
Bin
B
Cao
Ming-Zhi
MZ
Su
Feng-Xi
FX
Wang
Yong-Sheng
YS
He
Ping-Qing
PQ
Di
Gen-Hong
GH
Shen
Kun-Wei
KW
Wu
Jiong
J
Lu
Jin-Song
JS
Luo
Jian-Min
JM
Liu
Xiao-Yi
XY
Zhou
Jie
J
Wang
Lei
L
Zhao
Lin
L
Liu
Yan-Bing
YB
Yuan
Wen-Tao
WT
Yang
Lin
L
Shen
Zhen-Zhou
ZZ
Huang
Wei
W
Shao
Zhi-Ming
ZM
D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D012008:Recurrence