BRCA 1/2 genetic mutations are a known risk factor of breast cancer, but some individuals who are predisposed to the disease remain cancer-free.
To find out why this may occur, investigators sought to examine the genome variation in women with the BRCA 1/2 mutations and in whom early-onset breast cancer had not developed.
The results of the preliminary study, published in the New England Journal of Medicine
, showed that some of the women with BRCA 1/2 genetic mutations also had the co-occurrence of a rare COMT genetic variant.
“Not all mutation carriers develop the disease and the underlying reasons for this should be looked at, particularly with the large data sets now available to researchers,” said senior author Anelia Horvath.
The findings highlight the need to assess the genetic role of COMT in cancer, potentially through noncoding mechanism, the authors noted.
“We do not claim the variant is preventative of breast cancer in BRCA 1/2 carriers
; further research is needed to make those claims,” said senior author Anelia Horvath. “What we have done is illustrate a strategy for looking at the many data sets available for scientists today to look at different genes, different mutations, and discover patterns for why someone may never develop the disease predisposed by their high-risk mutation.”
Limitations to the study included: inaccessibility to the individual ages of the BRCA 1/2 carriers, so average age metrics targeted at the age during and after the age range of early onset of breast cancer were used; the BRCA 1/2 mutation spectrum differs between patients with breast cancer in the study and carriers of the mutation in the general population; to control for mutation types, the study focused exclusively on truncating variants; and insufficient information on the race and ethnic groups of the BRCA 1/2 carriers.
“Despite the current limited accessibility of incidentally discovered BRCA 1/2 carriers, our study suggests an intriguing genetic correlation,” the authors concluded. “Most importantly, it shows a new strategy to discover naturally occurring protective genetic signatures. This strategy is applicable to other genetic disorders and is now enabled by the increasing availability of population genomic data.”