There appears to be more variants of unknown significance in the BRCA2 gene compared with the BRCA1 gene in a population of Indonesian women with breast cancer, according to a new study presented at the European Society for Medical Oncology (ESMO) Asia 2016 Congress.

The authors argue that because such a high prevalence of variants of unknown significance cause uncertainty in patients, establishing a national database of such genetic mutations may be useful.

For the experiment, 41 female patients diagnosed with breast or ovarian cancers were recruited from two different medical centres in Jakarta, Indonesia. Because the study investigated the BRCA1 and BRCA2 genes, breast cancer patients recruited had to be below the age of 50. No age restrictions were imposed for ovarian cancer patients.

Other criteria for inclusion included having a family history of bilateral breast cancer, having a family history of male breast cancer, early-onset patients (<35 years of age) with no family history, and having a non-affected family member with a first-to-second-degree family member <50 years with breast cancer or ovarian cancer.

Each participant, after obtaining informed consent, was interviewed for family history and other relevant information including non-genetic risk factors. ?These information were used for pedigree construction.

Blood samples were collected from each participant and were subjected to direct sequencing for the analysis of the BRCA1 and BRCA2 mutation analysis. Finally, samples from some patients were also processed through Multiplex Ligation-dependent Probe Amplification.

From the analyses, it was found that there were more variants in BRCA2 than in BRCA1. There were 47 documented variants of BRCA2 found in 21 of the 41 patients. Interestingly, all variants found were classified as variants of unknown significance.

Further, there were four novel variants of BRCA2, including c.6718C>G, c.4490T>C, c.10176C>G and c.3281A>G. These were all found in four unrelated patients, each with their own family histories of breast cancer.

On the other hand, only six variants of the BRCA1 gene were found in seven patients who were not related to each other. In particular, one participant exhibited deleterious mutations on the 15^th exon of the BRCA1 gene.

Thus, the findings show that there are more variants of unknown significance in BRCA2 than in BRCA1, consistent with other studies in Asian populations. Further studies, particularly those that survey larger populations, are needed to determine the involvement of such mutations in breast cancer.