BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives

被引:118
作者
Lalloo, F
Varley, J
Moran, A
Ellis, D
O'Dair, L
Pharoah, P
Antoniou, A
Hartley, R
Shenton, A
Seal, S
Bulman, B
Howell, A
Evans, DGR
机构
[1] St Marys Hosp, Dept Clin Genet, Manchester M13 0JH, Lancs, England
[2] St Marys Hosp, Acad Univ Med Genet, Manchester M13 0JH, Lancs, England
[3] Christie NHS Trust, CR UK Paterson Inst Canc Res, Manchester, Lancs, England
[4] NW Canc Registry, Manchester, Lancs, England
[5] Guys Hosp, London SE1 9RT, England
[6] Univ Cambridge, Dept Oncol, Strangeways Res Labs, Cambridge CB2 1TN, England
[7] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England
[8] Christie NHS Trust, Canc Genet Dept, Manchester, Lancs, England
[9] Christie NHS Trust, Dept Med Oncol, Manchester, Lancs, England
关键词
BRCA1; BRCA2; TP53; familial breast cancer; family history;
D O I
10.1016/j.ejca.2005.11.032
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pathological mutations in BRCA1, BRCA2 and TP53 are associated with an increased risk of breast cancer. This study evaluated mutation frequency of these genes in early-onset breast cancer patients, and correlated this with family history and determined relative risks to family members. Patients with breast adenocarcinoma diagnosed <= 30 years were ascertained between 1980 and 1997. Family history was established and mutation screening of BRCA1, BRCA2 and TP53 genes was performed. Estimates of penetrance and relative risk were undertaken. DNA was obtained from 100/139 women. 17/36 familial cases had a BRCA1, BRCA2 or TP53 mutation. Of 64 non-familial cases, one BRCA2, two BRCA1 and two TP53 mutations were detected. Penetrance estimates (by age 70) for breast cancer were 84% for BRCA1 mutations and 91% for BRCA2 mutations and for ovarian cancer, 60% and 26%, respectively Relative risks associated with mutations were consistent with previous studies. BRCA1 and BRCA2 mutations in patients with breast cancer <= 30 years are predicted strongly by family history. The majority of families with ovarian cancer were due to mutations in BRCA1/2 whereas these mutations only accounted for 30-50% of the excess breast cancers. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1143 / 1150
页数:8
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