Meta-Analysis of BRCA1 and BRCA2 Penetrance

American Society of Clinical Oncology (ASCO) - Tập 25 Số 11 - Trang 1329-1333 - 2007
Sining Chen1, Giovanni Parmigiani1
1From the Departments of Environmental Health Sciences and Biostatistics, Johns Hopkins Bloomberg School of Public Health; and the Department of Oncology Biostatistics and Pathology, Johns Hopkins University, Baltimore, MD

Tóm tắt

Purpose Genetic counseling is now routinely offered to individuals at high risk of carrying a BRCA1 or BRCA2 mutation. Risk prediction provided by the counselor requires reliable estimates of the mutation penetrance. Such penetrance has been investigated by studies worldwide. The reported estimates vary. To facilitate clinical management and counseling of the at-risk population, we address this issue through a meta-analysis. Methods We conducted a literature search on PubMed and selected studies that had nonoverlapping patient data, contained genotyping information, used statistical methods that account for the ascertainment, and reported risks in a useable format. We subsequently combined the published estimates using the DerSimonian and Laird random effects modeling approach. Results Ten studies were eligible under the selection criteria. Between-study heterogeneity was observed. Study population, mutation type, design, and estimation methods did not seem to be systematic sources of heterogeneity. Meta-analytic mean cumulative cancer risks for mutation carriers at age 70 years were as follows: breast cancer risk of 57% (95% CI, 47% to 66%) for BRCA1 and 49% (95% CI, 40% to 57%) for BRCA2 mutation carriers; and ovarian cancer risk of 40% (95% CI, 35% to 46%) for BRCA1 and 18% (95% CI, 13% to 23%) for BRCA2 mutation carriers. We also report the prospective risks of developing cancer for currently asymptomatic carriers. Conclusion This article provides a set of risk estimates for BRCA1 and BRCA2 mutation carriers that can be used by counselors and clinicians who are interested in advising patients based on a comprehensive set of studies rather than one specific study.

Từ khóa


Tài liệu tham khảo

10.1200/JCO.2003.07.007

10.1002/1097-0142(19940201)73:3<643::AID-CNCR2820730323>3.0.CO;2-5

Chen S, Wang W, Broman K, et al: BayesMendel: An R environment for Mendelian risk prediction. Stat Appl Genet Mol Biol 3: Article 21, 2004

10.1038/sj.bjc.6602175

10.1016/0197-2456(86)90046-2

10.1086/301749

10.1002/ajmg.1320560305

10.1056/NEJM199705153362001

Hopper J, Southey M, Dite G, et al: Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in and : Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev 8:741,1999-747, BRCA1 BRCA2

Satagopan J, Offit K, Foulkes W, et al: The lifetime risks of breast cancer in Ashkenazi Jewish carriers of and mutations. Cancer Epidemiol Biomarkers Prev 10:467,2001-473, BRCA1 BRCA2

Satagopan J, Boyd J, Kauff N, et al: Ovarian cancer risk in Ashkenazi Jewish carriers of and mutations. Clin Cancer Res 8:3776,2002-3781, BRCA1 BRCA2

Scott CL, Jenkins MA, Southey MC, et al: Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in and estimated from multiple-case breast cancer families attending Australian family cancer clinics. Hum Genet 112:542,2003-551, BRCA1 BRCA2

10.1086/375033

10.1126/science.1088759

10.1038/sj.ejhg.5201256

10.1200/JCO.2005.03.6772

10.1136/jmg.2004.024133

10.1093/jnci/94.16.1221

10.1086/301670

Thông tin
Thông tin xuất bản

American Society of Clinical Oncology (ASCO)

Tập 25 Số 11

1329-1333

Thông tin tác giả