An international group led by researchers from the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have discovered associations between pathogenic variants of the BRCA 1 and 2 genes and four types of cancer. Published in ESMO Open, the findings expand the potential for personalized medicine to several cancer types that currently have limited treatment options and poor prognoses.
Pathogenic variants of the BRCA genes are well known to be associated with the risk of breast cancer, as well as ovarian, pancreatic, and prostate cancer. As a result, personalized medicine for these types of cancer using PARP inhibitors—a type of drug that kills cancer cells by preventing them from repairing their DNA—or certain chemotherapeutic drugs has become routine in clinical practice. For most other less common cancers, the BRCA association has yet to be studied. The goal of the new study was to fill in this missing information gap and determine whether the potential for BRCA-based personalized medicine exists for other types of cancer.
To start with, the researchers performed a case-control analysis of 3,489 patients whose data was taken from BioBank Japan, a multi-institutional, hospital-based registry of blood samples from all over Japan taken between 2003 and 2018. This type of analysis involves looking at people with and without a particular disease and identifying factors that could have led to different clinical outcomes. In this case they focused on nine types of cancer that have yet to be tested for a BRCA-gene association, namely bladder, bone, brain, head and neck, sarcoma, skin, testis, thyroid, and ureteral cancer. They compared the BRCA variants of the patients with those of 38,842 individuals from the same database who did not have cancer.
From the analysis, they found that pathogenic variants in BRCA1 increase the risk of thyroid cancer, while pathogenic variants in BRCA2 increase the risk of bladder cancer, head and neck cancer, and skin cancer. For bladder cancer, they found that the impact of BRCA2 pathogenic variants on cancer risk was greater in women than in men.
In the world of medical research, resources, both funding and manpower, are often skewed toward the most common and most deadly diseases. As a result, people with less common diseases are often out of luck when it comes to clinical trials or new treatment options. According to Hajime Sasagawa, the first author of the paper, “While previous studies have expanded the cancer risk profile associated with BRCA1/2 pathogenic variants to ovarian, pancreatic, and prostate cancer, we felt that relatively less common cancer types would also benefit from an expansion of genetic evidence, particularly because of their limited treatment options and poor prognoses. I am happy that we were able to gain these new insights.”
According to Yukihide Momozawa, the corresponding author of the study, “I am happy that we have been able to gain these new insights. Although this study will not lead to immediate recommendations for active surveillance of those cancer types, we hope that these findings will contribute to the development of personalized medicine guidelines for these four types of cancer.”
Previous to the current study, the group has revealed a number of new BRCA-related cancers in a study published in JAMA Oncology in 2022 and on genome and environmental interactions in the New England Journal of Medicine in 2023.