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More Genetic Insights Into 3 Types of Cancer
Date:3/27/2013

By Barbara Bronson Gray
HealthDay Reporter

WEDNESDAY, March 27 (HealthDay News) -- Critical clues to understanding who is at the greatest risk for particular types of cancer may be found in "spelling mistakes" contained in a person's DNA.

In a step toward personalized medicine and the ability to better understand individual risk factors for three common hormone-related cancers, a large team of international researchers have unveiled what might be the clearest picture to date of the genetic alterations associated with some forms of the disease.

Although more research is needed, the study authors predict that genetic testing to help determine a person's risk for some of the most potentially deadly cancers may be available within five to 10 years.

"We think the most immediately practical application will be in people already at risk for the disease and going through the genetic counseling process," said Douglas Easton, a professor of genetic epidemiology at the University of Cambridge, in England.

A combination of five studies that include work from 160 different research groups has identified more than 80 genetic errors that are linked to increased risk of breast, prostate and ovarian cancers. The research was published March 27 in the journal Nature Genetics.

More than 2.5 million people worldwide are diagnosed with these three types of cancers each year, according to the researchers.

Everyone has some of the so-called spelling mistakes, often called "snips" (single nucleotide polymorphisms, or SNPs), the researchers said. Problems are signaled by errors in the sequence of genetic elements (bases), where letters representing the elements -- A, G, C and T -- are incorrectly placed.

The sequence of bases in a portion of a DNA molecule, called a gene, carries the instructions that are needed to create a protein. Although some errors affect small things, others may be responsible for increasing vulnerability to certain forms of cancer. The impact on a person depends on where on the strand of DNA the genetic alteration is located.

The studies from the European-based consortium -- collectively known as the Collaborative Oncological Gene-Environment Study, or COGS -- compared 100,000 patients with breast, ovarian or prostate cancer to 100,000 healthy people.

The massive collaboration involved more than 130 institutions for the breast cancer study, more than 100 institutions for the ovarian cancer study and 70 for the prostate cancer study.

Researchers did genetic analyses of all the participants, studying 200,000 particular sections of the DNA strand. Certain variations were associated with increased risk of disease. For example, researchers found the following:

  • Breast cancer: 49 spelling mistakes (SNPs), more than double what had previously been discovered
  • Prostate cancer: 26 new deviations, which adds up to a total of 78 SNPs now linked to the disease
  • Ovarian cancer: Eight new SNPs associated with this form of cancer

What's more, the scientists identified DNA regions that suggest a shared genetic basis and mechanism among all three cancers. "There were clearly a number of regions where you get SNPs for more than one cancer," Easton said. "There are a number of other regions where we presume there are particular genes important for a range of cancer types."

Implications of the enormous research effort are far ranging, the scientists said. As the precise role of genetics in cancer is better understood, lifestyle factors will continue to be seen as critical, even in cancers that are considered closely tied to genetics, said Dr. Paul Pharoah, a senior clinical research fellow at the University of Cambridge.

"It's quite clear from what [we] understand about the genetics of these cancers that the lifestyle or environment act in concert with the genetics," Pharoah said. "So whatever your level of genetic risk, it's influenced by lifestyle. It's clearly wrong to think of the genetic component as in any way deterministic."

Understanding how this research will play out in terms of screening, prevention and treatment will require more research, ideally by an international effort similar in scale to the COGS studies, the authors wrote.

A commentary published with the studies, written by Pharoah and others, explored the possibilities of how this sort of genetic analysis could make prevention and treatment programs more complex.

"First, appropriate systems for inviting and recalling people for risk assessment and screening need to be in place," the authors wrote. "Second, there should be a standard protocol for taking consent, performing genetic sampling and using a standardized risk-assessment tool to integrate genetic data from an individual with environmental, lifestyle and hormonal data."

Ultimately, a person's level of risk of cancer will dictate what care and treatments will be offered, they concluded.

More information

Learn more about cancer and genetics from the U.S. National Cancer Institute.

SOURCES: Douglas Easton, Ph.D., professor of genetic epidemiology, University of Cambridge, England; Paul Pharoah, M.D., senior clinical research fellow, University of Cambridge; March 27, 2013, Nature Publishing Group press conference; March 27, 2013, Nature Genetics


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