April 4, 2013

Cancer studies reveal new genetic variants

The future of cancer is becoming clearer. And it’s not looking so good for cancer.

The future of cancer is becoming clearer. And it’s not looking so good for cancer.

In a series of papers published last week, several international teams of scientists, including researchers at Vanderbilt University, reported the discovery of more than 70 new genetic variations associated with cancers of the breast, prostate and ovaries.

These variations, also called single nucleotide polymorphisms or SNPs, were found by genotyping, or scanning genetic material provided by more than 200,000 different individuals. This powerful approach to cancer gene discovery is called the “genome-wide association study.”

The newly discovered SNPs, along with those identified previously, explain up to one third of the inherited risk for each cancer. Down the road, these SNPs could be used to develop new screening tests, for example, for people with a family history of these hormone-related cancers.

These variations and where they’re located on the genome also reveal new insights about how cancers develop, and suggest potential targets for new, more effective drugs to treat and even prevent them from occurring in the first place.

Wei Zheng, M.D., Ph.D., MPH

“That’s why it’s so exciting,” said Wei Zheng, M.D., Ph.D., MPH, professor of Medicine, chief of the Division of Epidemiology and director of the Vanderbilt Epidemiology Center. In the future, “we can more precisely guide through people prevention, diagnosis and treatment. We’re not there yet, but we’re working on it.”

In total, 13 papers were published online March 27; five in Nature Genetics, three in PLoS Genetics; two each in Human Molecular Genetics and Nature Communications; and one in The American Journal of Human Genetics.

Vanderbilt researchers contributed to nine of the papers, and Zheng was lead author of a paper in Human Molecular Genetics that evaluated common genetic determinants of breast cancer risk in women in China, Korea, Japan, Malaysia, Thailand and other East Asian countries.

Most previous studies have involved people of European descent. However, risk variants identified in European descendants may not be relevant for other populations, Zheng noted.

The Vanderbilt study was the largest conducted to date in East Asian women, with about 50,000 participants. The researchers examined 67 genetic regions previously associated with breast cancer susceptibility in European women, and found that about half — but not all — could be directly replicated in East Asians.

There is increasing evidence that screening patients for these variants may improve the ability to determine their risk of developing certain cancers or relapsing after initial treatment.

“We need to identify more risk variants to improve the utility of screening tests using genetic markers,” Zheng said. “We’re not at that point yet, but these additional markers are a step in the right direction.”

While Vanderbilt, through its personalized medicine initiative, is uniquely positioned to contribute to these studies, he said, they “can only be done with these kinds of big, big collaborations.”

This gargantuan effort by hundreds of scientists around the globe, this “moonshot against malignancy,” could not have been achieved without consistently strong support from the U.S. government and governments around the world, as well as private foundations and the biotech and pharmaceutical industries, the researchers added.

In addition to Zheng, nine other Vanderbilt faculty, representing the Division of Epidemiology, the Vanderbilt Epidemiology Center and the Vanderbilt-Ingram Cancer Center, contributed to the papers published last week.

The Vanderbilt-led study was supported primarily by National Institutes of Health grants CA124558, CA148667, CA064277, CA070867 and CA148065, as well as Ingram Professorship funds.