With a negative test for BRCA2 mutations, not everyone should relax
Women with certain mutations of the BRCA1 or BRCA2 genes are at high risk for developing breast cancer. Traditionally, in the absence of a woman with such a family history of the corresponding mutation, her risks are equated with the risks of the general population.
However, the data obtained by scientists at the University of Manchester, working under the guidance of Professor Gareth R. Evans, refute this assumption. The study showed that even in the absence of corresponding BRCA2 mutations, the risk of developing breast cancer in women with a family history of mutations of this gene is more than 4 times higher than the average population. This dependence is most pronounced in families with a large number of cases of the disease and the presence of other genetic risk factors.
The authors analyzed data collected earlier during a study in which families of patients with breast and/or ovarian cancer were screened for BRCA1 and BRCA2 gene mutations. As a result, they found 49 women in 807 families with a history of mutations of these genes, who, despite the negative results of genetic testing, subsequently developed breast cancer.
When dividing women into age groups (30-39, 40-49, 50-59 and 69-80 years), it turned out that in each of the groups there were 2 times more cases of the disease than could be expected for the general population of women at the same age.
After that, the authors conducted a risk analysis. To do this, they calculated the "observed to expected ratio", that is, the ratio of the risk of developing breast cancer in BRCA-negative women from families at risk and the average population risk.
It turned out that for women from families with BRCA1 gene mutations, this risk practically did not differ from the average population, whereas for women from families with BRCA2 gene mutations, the risk exceeded the average population by 4.57 times.
According to the authors, it is most likely that in addition to the genes of the BRCA family, women inherit some other genetic factors that increase the risk of developing breast cancer. To date, approximately 77 single nucleotide polymorphisms (snips) associated with breast cancer are known. To explain the reasons for the revealed pattern, it is apparently necessary to identify additional snips.
The authors also warn specialists that it is necessary to determine with caution the level of risk of breast cancer in women from families with BRCA2 gene mutations, because, even despite the negative results of genetic testing, their risks may be significantly higher than the average population, especially if there are a large number of cases of the disease in the family history.
Article by D. Gareth R. Evans et al. Increased Rate of Phenocopies in All Age Groups in BRCA1/BRCA2 Mutation Kindred, but Increased Prospective Breast Cancer Risk Is Confined to BRCA2 Mutation Carriers published in the journal Cancer Epidemiology, Biomarkers & Prevention.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the American Association for Cancer Research:
Negative BRCA Testing May Not Always Imply Lowered Breast Cancer Risk.
04.12.2013