Probability of Carrying a Mutation of Breast-Ovarian Cancer Gene BRCA1 Based on Family History

Abstract

This model focuses on mutations in BRCA1 and assumes that all other breast cancer is sporadic. With the cloning of BRCA2, we now know that this assumption is incorrect. We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1. The current model is, nevertheless, appropriate and useful. Of principal importance is its potential and that of improved versions for aiding women and their health care providers in assessing the need for genetic testing.

RASSF1APolymorphism A133S Is Associated with Early Onset Breast Cancer inBRCA1/2Mutation Carriers

“…To determine whether the A133S polymorphism is associated with familial breast cancer independent of BRCA1/2 status, we further divided the non-BRCA1/2 mutation carriers into two groups [higher familial breast cancer risk group (n = 223) and lower familial breast cancer risk group (n = 172)] using BRCAPRO, a computer model designed to calculate the predisposition of an autosomal dominant familial breast cancer phenotype (16,17). As shown in Table 2, A133S is more frequent in patients in the higher familial breast cancer risk group (23.3%, P = 0.029; OR, 1.76; 95% CI, 1.06-2.92) compared with the controls.…”

A probability model for predicting BRCA1 and BRCA2 mutations in breast and breast-ovarian cancer families

“…Several probability models for mutation detection have been developed. These are, however, based only on BRCA1 (Berry et al, 1997;Couch et al, 1997;Shattuck-Eidens et al, 1997), focus on specific founder mutations in the Ashkenazi population (Foulkers et al, 1999;Hodgson et al, 1999;Hopper and Jenkins, 1999), or require information such as penetrance estimations not available in all populations (Berry et al, 1997;Parmigiani et al, 1998; ChangClaude et al, 1999).Here we have developed a model for predicting the presence of a BRCA1 or BRCA2 mutation in families with 3 or more relatives affected with breast or ovarian cancer. We also compared this model with those of Shattuck-Eidens et al (1997) and Couch et al (1997) originally designed for BRCA1 only.…”

“…Several probability models for mutation detection have been developed. These are, however, based only on BRCA1 (Berry et al, 1997;Couch et al, 1997;Shattuck-Eidens et al, 1997), focus on specific founder mutations in the Ashkenazi population (Foulkers et al, 1999;Hodgson et al, 1999;Hopper and Jenkins, 1999), or require information such as penetrance estimations not available in all populations (Berry et al, 1997;Parmigiani et al, 1998; ChangClaude et al, 1999).…”

Validity of Models for Predicting BRCA1 and BRCA2 Mutations

“…We used a version of the BRCAPRO (13,14) model based on the genetic variables described by Iversen and colleagues (42).…”

“…The demand for assessment of complex family histories of cancer has led to widespread use of statistical models to estimate mutation probabilities (2,(10)(11)(12)(13)(14)(15)(16)(17)(18). Model-based predictions are currently used in counseling about genetic testing, are included in materials distributed to women considering genetic testing (18)(19)(20)(21), are used for determining eligibility for screening and prevention studies (22), and are factored into coverage decisions by insurers (23).…”