PATHOGENIC variants in BRCA1 and BRCA2 are associated with a broader range of cancer types than previously determined, a large-scale case-control study has found. BRCA1 and BRCA2 are tumour suppressor genes, which help regulate cell division. However, pathogenic variants of these genes have been linked with a much higher risk of developing breast, ovarian, or other types of cancers.
The research consisted of a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years; 42% female) and 37,086 controls, using data from a multi-institutional hospital-based Japanese biobank. The registry data was analysed to estimate the risk of each cancer type, to establish the specific clinical characteristics related to pathogenic variant carrier status, and finally to examine how useful family history is in identifying patients with pathogenic variants.
The study identified 300 pathogenic variants. The authors found that biliary tract cancer was linked to pathogenic variants in BRCA1, oesophageal cancer to variants in BRCA2, and gastric cancer to variants in BRCA1 and BRCA2. Two more cancer types were linked to BRCA1, and four to BRCA2. Enrichment of carrier patients was also shown in ovarian, female breast, prostate, and biliary tract cancers, in accordance with an increased number of such cancer types in the family history.
Commenting on the importance of their findings, first author Yukihide Momozawa, Team Leader at the Laboratory for Genotyping Development, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan, stated: “These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [polyadenosine diphosphate-ribose polymerase] inhibitors for each cancer type.” Momozawa went on to add: “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”
