No Sib Pair Concordance for Breast or Ovarian Cancer in BRCA1 Mutation Carriers

Breast and ovarian cancers are both expressions of BRCA1 germ-line mutations. There have been speculations whether or not modifying factors may determine whether a mutation carrier contracts breast or ovarian cancer. There are reports on environmental factors having such effects in the population and/or in BRCA1 mutation carriers (oral contraceptives, etc.) [1,2], natural variations in sex hormones (childbirth, etc.) [3], and also lifestyle [4]. Germline BRCA1 mutations (OMIM +113705) cause breast and/or ovarian cancer. Besides sex and highly penetrant mutations, there are no described major predictor factors determining who is to contract breast cancer, or when she might do so. Whether the position of the mutation within each gene is indicative of what kind of cancer a BRCA mutation carrier may contract has been discussed [5-7].The possibility of genetic modifiers of expression of BRCA1 mutations is important for three reasons:1. Does a BRCA1 mutation carrying sister or daughter to an ovarian or breast cancer patient have higher risk for ovarian or breast cancer, respectively, than other BRCA1 mutation carrying women? Such questions are frequently asked during genetic counselling. Because health care with respect to oophorectomy and mastectomy is a personal choice, lack of evidence may lead to intervention based on unsubstantiated fear. Besides the obvious problems with decision making in the absence of knowledge, the fear itself may be considered a health problem.2. The other question is cost/benefit of research programmes to look for modifiers of penetrance or expression of BRCA1 mutations.3. The third question is whether the family history may indicate which mutations to look for when performing mutational analyses in a new family.Also, if there are environmental factors influencing BRCA1 expression, they should be present and subject to identification within concordant pairs. If so, this may be a way to identify behaviour patterns to avoid contracting breast or