Scientists home in on breast-cancer genetics

In a long-delayed harvest from the human genome project, researchers say they have found six new sites of variation in the genome that increase the risk of breast cancer.

Together with already-known genes, the discovery means that a sizable fraction of the overall genetic risk of breast cancer may now have been accounted for, researchers say, and much of the rest could be captured in a few years.

The findings do not point to any new treatment and are too little understood to serve as the basis of a diagnostic test. But they are a critical step toward understanding the biology of breast cancer, scientists say, from which new treatments should emerge.

Understanding the genetic basis of common disease was the promised payoff of the $3 billion human genome project, which was completed in 2003 but has taken some time to show many tangible results. The logjam seems to be breaking. Last month, seven new DNA variations associated with diabetes were discovered, and advances with other diseases are expected to be announced soon.

The new findings have been made possible by new instruments, known as chips, which enable up to 500,000 points of variation on the human genome to be tested simultaneously for possible association with disease. But to attain statistical strength, large numbers of patients must be recruited, which has prompted otherwise competitive groups to work together.

Using the new chips, scientists can compare breast cancer patients with healthy individuals, looking for variant sites on the DNA of the human genome that seem associated with the disease. Because the chips sample each patient's entire genome, the new approach is known as a whole genome association study.

With this approach, a large consortium of breast cancer scientists, led by Douglas F. Easton of the Cancer Research-UK Genetic Epidemiology Unit in Cambridge, England, says it has found five new sites on the genome where a common variation confers a risk of breast cancer. Their findings were reported Sunday in the journal Nature.

Two of the same sites of variation have been found by a second team, led by David Hunter of the Harvard School of Public Health. Decode Genetics, a gene-finding company based in Iceland, has also identified two new sites of variation, one of which is the same as one found in Easton's study. The reports from Hunter and Decode Genetics were published online in the journal Nature Genetics.

Scientists involved in the three studies expressed confidence that most of the genetic risk of breast cancer will be detected through the whole genome association approach. "Once the dust has settled, yes, it's possible we may have captured most of the genetic variation," Easton said.