Gene sequences associated with breast and ovarian cancer identified
26 March 2013
Three studies reported in Plos Genetics and Nature Genetics have
found new DNA sequences associated with breast cancer and ovarian
cancer. The findings could help reveal the underlying causes of
these diseases and help researchers build better risk models to
support new prevention strategies.
In the first study, published in the journal PLoS Genetics,
researchers studied variations across the genomes of 14,351 BRCA1
mutation carriers and found two new DNA sequences that are
associated with breast cancer risk and two new DNA sequences
associated with ovarian cancer risk. One sequence associated with
ovarian cancer is the first known BRCA1-specific risk sequence for
the disease. The researchers were then able to use their results to
estimate the risks of both cancers for each BRCA1 mutation carrier.
These new results may soon be incorporated into clinical management
“Women with mutated copies of the BRCA1 or BRCA2 gene have
markedly increased but highly variable risks of breast and ovarian
cancer,” says Fergus Couch, Ph.D., a Mayo Clinic investigator who
co-authored the study. “To put this into perspective, a woman with a
BRCA1 mutation has about a 65%t lifetime risk,” says Dr. Couch.
“Risk models will help her make decisions by indicating if her true
risk is liable to be closer to 90% — in which case she may choose
prophylactic surgery — or closer to 40% — in which case frequent
monitoring may be most appropriate.”
The second study, published in the journal Nature Genetics,
focuses on women susceptible to estrogen receptor-negative
(ER-negative) forms of breast cancer. Dr. Couch’s team discovered
four new DNA sequences that were associated with ER-negative breast
cancer but not ER-positive breast cancer. The discovery was based on
integrated results from three genome-wide association studies of
6,514 ER-negative breast cancer patients and 41,555 healthy
“Women have a worse prognosis if their tumours are ER-negative
because these cells grow more rapidly,” says Dr Couch. “They also
have fewer treatment options.” He says the new DNA sequences will
yield new information about the biology of the disease, which could
eventually help researchers develop new treatments.
About one fourth of all breast cancers are ER-negative, with a
higher proportion in younger women and women of African ancestry.
ER-negative breast cancers are more aggressive and unresponsive to
anti-estrogens compared to ER-positive breast cancers, which
generally have a better prognosis and are often responsive to anti-estrogen
The third study, also published in Nature Genetics, reports the
findings of the largest genome-wide association study in any cancer
to date. Researchers found 41 new DNA sequences associated with
breast cancer. Incorporating the DNA sequences into risk models is
expected to significantly improve the ability to predict which women
are at greater risk of developing breast cancer.
The researchers, including Dr. Couch and authors from Cambridge
University’s Centre for Cancer Genetic Epidemiology, integrated
information from more than 30,000 breast cancer patients and more
than 30,000 healthy controls.
The Mayo studies are part of the Collaborative Oncological
Gene-environment Study (COGS), an international research
collaboration involving investigators from Europe, Asia, Australia
and North America, which identified 49 new DNA sequences associated
with an increased risk for breast cancer, ovarian cancer and
prostate cancer. “This was an unprecedented study of genetic and
lifestyle factors that involved the genotyping of more than 250,000
individuals by 117 research institutes around the world,” says Dr.
Couch. “The studies were so large that the results are really