By Elodie Vaz | Published on April 22, 2026
| 3 min read
Mutations in the BRCA1
and BRCA2 genes have historically been associated with an increased risk of
breast and ovarian cancers, as well as pancreatic and prostate cancers. These
genes play a key role in DNA repair, and their pathogenic variants impair this
mechanism, promoting the accumulation of genetic abnormalities and cellular
transformation. This understanding has enabled the development of personalized
medicine strategies, particularly through the use of PARP inhibitors. However,
for many rarer cancers, the involvement of these genes has remained largely
unexplored.
In this context, an
international team led by the RIKEN Center for Integrative Medical Sciences
(IMS) sought to fill this knowledge gap in a study published in April in the
journal ESMO Open. The aim was to determine whether pathogenic variants
in BRCA1 and BRCA2 might also be involved in other types of cancer, thereby
opening the door to new applications of personalized medicine. “While previous
studies have expanded the cancer risk profile associated with BRCA1/2
pathogenic variants […] we were convinced that less common cancers would also
benefit from deeper genetic investigation,” said Professor Hajime Sasagawa,
first author of the study.
Exploring
often-overlooked cancers
The researchers conducted
a case-control study using data from BioBank Japan, including 3,489 cancer
patients and 38,842 control individuals. The data, collected between 2003 and
2018, come from a large multi-institutional hospital registry. The analysis
focused on nine types of cancer whose association with BRCA genes had not yet
been clearly established: bladder, bone, brain, head and neck, sarcomas, skin,
testicular, thyroid, and ureter cancers.Patients’ genetic profiles were
compared with those of controls to identify significant correlations between
BRCA variants and the occurrence of these cancers.
The results reveal new
associations. Pathogenic variants in the BRCA1 gene are linked to an increased
risk of thyroid cancer. Meanwhile, BRCA2 variants significantly increase the
risk of bladder, head and neck, and skin cancers. Notably, in the case of bladder
cancer, this risk appears higher in women than in men.
These findings
considerably broaden the spectrum of cancers associated with BRCA mutations and
suggest that common mechanisms of defective DNA repair may be involved in these
conditions, which had not previously been linked to these genes.
Thyroid, skin,
bladder… new links uncovered
This study represents an
important step forward in understanding rare cancers and their management. It
suggests that personalized medicine approaches already used for breast or
ovarian cancers could be extended to other indications, often characterized by
poor prognosis and limited therapeutic options.
As Professor Yukihide
Momozawa, senior author, notes: “Although this study does not immediately lead
to clinical recommendations […] we hope that these findings will contribute to
the development of personalized medicine guidelines for these four cancer types.”
Ultimately, this work
paves the way for future targeted clinical trials and better integration of
genetic profiles into the management of rare cancers, laying the groundwork for
a more inclusive precision oncology.
Read next: Breast
cancer: circulating tumor DNA, a key biomarker to anticipate relapse
About the Author –
Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on
human life. A registered nurse since 2010, she spent twelve years at patients’
bedsides before exchanging her stethoscope for a notebook. She now investigates
the links between environment and health, convinced that the vitality of life
cannot be reduced to that of humans alone.
