Sequencing Cancer's DNA May Yield Better Prevention Strategies
March 28, 2013

New DNA Sequences Help Reveal Underlying Causes Of Breast, Ovarian Cancer

redOrbit Staff & Wire Reports - Your Universe Online

Researchers at the Mayo Clinic Cancer Center have identified new DNA sequences associated with breast and ovarian cancers that help reveal the underlying causes of these diseases so new prevention strategies can be devised.

The findings appear in three studies in the journals PLoS Genetics and Nature Genetics.

In the first study, published in the journal PLoS Genetics, researchers looked at 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.

"Women with mutated copies of the BRCA1 or BRCA2 gene have markedly increased but highly variable risks of breast and ovarian cancer," said study co-author Fergus Couch, Ph.D. at the Mayo Clinic.

"To put this into perspective, a woman with a BRCA1 mutation has about a 65 percent lifetime risk," he said.

"Risk models will help her make decisions by indicating if her true risk is liable to be closer to 90 percent – in which case she may choose prophylactic surgery – or closer to 40 percent – in which case frequent monitoring may be most appropriate."

The findings may soon be incorporated into clinical management of patients, the Mayo Clinic said.

The second study, published in the journal Nature Genetics, focused on women susceptible to estrogen receptor-negative, or 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 controls.

"Women have a worse prognosis if their tumors are ER-negative because these cells grow more rapidly," said Dr. Couch.

"They also have fewer treatment options,” he said.

But the new sequences will yield new information about the biology of the disease, which could eventually help researchers develop new treatments.

About one-quarter of all breast cancers are ER-negative, with a higher proportion in younger women and women of African ancestry. ER-negative breast cancers are typically more aggressive and unresponsive to anti-estrogens compared with ER-positive breast cancers, which generally have a better prognosis and are often responsive to anti-estrogen therapy.

The third study, also published in Nature Genetics, reports the findings of the largest genome-wide association study in any cancer to date. 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, and identified 41 new DNA sequences associated with breast cancer. Incorporating these 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 Mayo Clinic said.

All of the current 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, ovarian 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," said Dr. Couch.

"The studies were so large that the results are really trustworthy."

Breast cancer is the most common cancer among women, with an average lifetime risk of developing the disease of 10 percent. Ovarian cancer is the most common cause of death from gynecological cancers in the US.