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Breast cancer is the most common cancer in women (excluding skin cancer). The risk of developing breast cancer in the normal population of the United States and Europe is 8%-10%. A family history of breast cancer is present in around 10% of overall cases. Breast cancer susceptibility genes BRCA1 and BRCA2 have recently been identified (Miki et al, 1994; Wooster et al, 1995). Both BRCA1 and BRCA2 are considered to be responsible for a similar proportion (40%) of inherited breast cancer (Bennett et al, 1999) but the majority (81%) of the breast-ovarian cancer families are due to BRCA1 whereas BRCA2 is found in the majority (76%) of families with male and female breast cancer (Ford et al, 1998). Carriers of BRCA1 or BRCA2 mutations from families with high cancer risk have been estimated to have an 85% lifetime risk of developing breast cancer (Bennett et al, 1999). In addition, BRCA1 mutations carriers have a 65% lifetime risk of developing ovarian cancer (Easton et al, 1995).
Family members at higher risk of breast cancer can now be tested to see whether they are BRCA1 or BRCA2 carriers. An individual who undergoes genetic counseling before testing can be told the probabilities that he or she is a carrier, given the family history.
BRCAPRO is a program, developed by G. Parmigiani, D.A. Berry and O. Aguilar at the Institute of Statistics and Decision Sciences, Duke University, U.S.A., which calculates the probability that a particular family member carries a germ-line mutation of the BRCA1 and BRCA2 genes. Although the method applies to both women and men, the proband is usually female. The calculations are based on Bayes rules of determination of the probability of a mutation, given family history. An estimate of the mutation frequencies in the normal population (Claus et al, 1996; Ford et al, 1998) and among Askenazi Jews (Struewing et al, 1997) provides the probability of the mutation in the proband, prior to the ascertainment of family history. The family history includes the proband and first- and second- degree relatives. No provision is made for inbreeding, monozygous twinning, or for other relatives. While for many families BRCAPRO will give a useful estimate of risk, there are some families where important information will not be used in the calculation. For each member of interest, it is important to ascertain whether he or she has been diagnosed with breast cancer and either the age at diagnosis or, if cancer free, the current age or the age at death. Unaffected members are important in the calculation, but only if their current age or age at death is known. The method assumes that individuals inherit two BRCA1/BRCA2 alleles, one from each parent, that alleles are either normal or mutated and that mutations are inherited independently through an autosomal dominant mode of inheritance. For detailed explanation of the method the user is referred to the authors publication (Parmigiani et al, 1998).
Examples for using BRCAPRO are provided in the Cyrillic manual. The Help files also contain more information.
BRCAPRO is developed by G Parmigiani, DA Berry and O Aguilar. The developers assume no legal liability for use of their software or algorithms.
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