Breast cancer risk may still be higher despite BRCA-negative test results

Women from families with a history of carrying the cancer risk gene BRCA2, but who test negative for it, may be at higher risk of breast cancer than previously thought.

Professor Gareth Evans of the University of Manchester, the lead author of the study, said it was 'likely that these women inherit genetic factors other than BRCA-related genes that increase their breast cancer risk'.

The researchers analysed data from 807 families with a history of carrying either the BRCA1 or BRCA2 gene mutation. Forty-nine women from these families tested negative for their family-specific mutation but went on to develop breast cancer.

The researchers noted four and a half times the number of breast cancers in non-carrier women from BRCA2 families than would be expected in women of the same age in the general population. However, the incidence of breast cancer in test-negative women from BRCA1 families was not significantly increased.

Professor Evans suggests that families who carry BRCA2 may be more likely to carry other cancer risk mutations.

'Around 77 single nucleotide polymorphisms (SNPs) are linked to breast cancer risk', he said. 'Identification of additional SNPs is necessary to understand why some of the BRCA-negative women from BRCA families are at higher risk'.

BRCA genes are 'tumour suppressor genes', encoding proteins that help the body repair damaged DNA. Inheriting faulty copies of these genes allows genetic damage to accumulate in cells, which might potentially lead to breast or ovarian cancer.

This new research may have implications for genetic counselling of women who test negative for BRCA2 mutations.

'Providing patients with accurate information on their risk of developing breast cancer in the future is critical for decision-making regarding different options and interventions', confirmed Dr Elisa Port, from the Dubin Breast Center in New York, USA, speaking to HealthDay News.