BRCA-Negative Results May Not Reduce Cancer Risk

Genetic changes in breast cancer genes are known to carry a higher risk, but even family members who test negative for the genetic differences are still at an increased probability of developing the disease.

The credence that a woman from a family with breast cancer gene (BRCA) mutations who tests negative for her family-specific BRCA mutation has the same chances of contracting the disease as someone in the general population has been challenged.


Scientists at the University of Manchester (UK) identified 807 BRCA families, including information about whether or not relatives had been tested. DNA was extracted from blood samples provided by women attending the genetic clinics. In addition to the BRCA1/2 mutation analysis, women were genotyped for 18 single nucleotide polymorphisms (SNPs) that have been shown to be associated with breast cancer risk in the general population and a subset of SNPs in familial breast cancer.

The investigators found that found that 49 women who had tested negative for the BRCA mutation had subsequently developed breast cancer. Even when the scientists factored in age, they found that in each age group, there were about twice as many cases of breast cancer as would be expected within the general population. Of the 49 women, 22 were among 279 women who tested negative from BRCA1 families, and 27 were among the 251 women who tested negative to BRCA2 mutations.

They also found that the women from BRCA1 families did not experience any increased risk, but the observed versus expected ratio (O/E) for women from BRCA2 families was 4.57 which led to the conclusion that BRCA-negative women from BRCA2 families face a fourfold increased risk of developing breast cancer.

Gareth R Evans, MD, FRCP, a professor and the lead author of the study said, “About 77 single nucleotide polymorphisms (SNPs), the genetic variations that can help track the inheritance of disease genes within families, are linked to breast cancer risk. Identification of additional SNPs is necessary to understand why some of the BRCA-negative women from BRCA families are at higher risk. If there is a strong family history of breast cancer in a BRCA2 family, for example with a mother and sister diagnosed under the age of 50, they should seek additional screening even if had tested negative previously.” The study was published on November 27, 2013, in the journal Cancer Epidemiology, Biomarkers & Prevention.

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