Log odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a Defined personal and family history in an Ashkenazi Jewish woman (LAMBDA)

Breast Cancer Research

John L Hopper¹  Deon J Venter⁴  Melissa C Southey⁴  Agnes Bankier²  Michael Friedlander⁵  Katherine Tucker⁵  Ellen Solomon³  Cathryn M Lewis³  Sheila A Fisher³  Shirley V Hodgson³  Lesley Andrews⁵  Carmel Apicella⁶ 

[1] Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Victoria, Australia;Victorian Clinical Genetics Service, Royal Children's Hospital, Parkville, Victoria, Australia;Division of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, London, UK;Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia;Prince of Wales Hospital, Randwick, New South Wales, Australia;Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia

关键词: ovarian cancer;    mutations;    breast cancer;    BRCA2;    BRCA1;    Ashkenazi Jews;   

Others  :  1118789
DOI  :  10.1186/bcr644

 received in 2003-05-30, accepted in 2003-07-31,  发布年份 2003

【 摘 要 】

Introduction

Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors.

Methods

We studied Ashkenazi Jewish women with a personal or family history of breast or ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous diagnosis of breast or ovarian cancer and living in the UK. DNA samples were tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2. Logistic regression was used to identify, and to estimate the predictive strength of, major determinants.

Results

A mutation was detected in 64 of 424 women. An algorithm was developed by combining our findings with those from similar analyses of a large study of unaffected Jewish women in Washington. Starting with a baseline score, a multiple of 0.5 (based on the logistic regression estimates) is added for each predictive feature. The sum is the estimated log odds ratio that a woman is a carrier, and is converted to a probability by using a table. There was good internal consistency.

Conclusions

This simple algorithm might be useful in the clinical and genetic counselling setting. Comparison and validation in other settings should be sought.

【 授权许可】

   
2003 Apicella et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

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