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New Genetic Clues to Breast Cancer?
Date:1/23/2012

By Kathleen Doheny
HealthDay Reporter

SUNDAY, Jan. 22 (HealthDay News) -- Researchers have identified three new genomic regions they believe are linked with breast cancer that may help explain why some women develop the disease.

All three newly identified areas "contain interesting genes that open up new avenues for biological and clinical research," said researcher Douglas Easton, a professor of genetic epidemiology at the University of Cambridge in England.

Breast cancer is the most common cancer among women, with about 1 million new cases annually worldwide and more than 400,000 deaths a year.

Scientists conducting genome-wide association studies -- research that looks at the association between genetic factors and disease to pinpoint possible causes -- had already identified 22 breast cancer susceptibility loci. Locus is the physical location of a gene or DNA sequence on a chromosome.

"The three [newly identified] loci take the number of common susceptibility loci from 22 to 25," said Easton.

However, the three new susceptibility loci might explain only about 0.7 percent of the familial risks of breast cancer, bringing the total contribution to about 9 percent, the researchers said.

Michael Melner, scientific program director for the American Cancer Society, said this current research adds some important new clues to existing evidence, but he agreed that the number of cases likely associated with these three variants is probably low.

"So the total impact in terms of patients would be fairly small," Melner said.

The study is published online Jan. 22 in Nature Genetics.

To find the new clues, Easton's team worked with genetic information on about 57,000 breast cancer patients and 58,000 healthy women obtained from two genome-wide association studies.

The investigators zeroed in on 72 different single nucleotide polymorphisms (SNPs). A SNP -- pronounced "snip" -- is a change in which a single base in the DNA differs from the usual base. The human genome has millions of SNPs, some linked with disease, while others are normal variations.

The researchers focused on three SNPs -- on chromosomes 12p11, 12q24 and 21q21.

Easton's team found that the variant on the 12p11 chromosome is linked with both estrogen receptor-positive breast cancer (which needs estrogen to grow) and estrogen receptor-negative breast cancer. The other two variants are only linked with ER-positive cancers, they said.

One of the newly identified variants is in an area with a gene that has a role in the development of mammary glands and bones. Easton said it was already known that mammary gland development in puberty is an important period in terms of determining later cancer risk. "But these are the first susceptibility genes to be shown to be involved in this process," he said.

One of the other SNPs is in an area that can affect estrogen receptor signaling, the researchers found.

Melner, noting some of the research is "fine tuning" of other work, said in his view the new understanding of the signaling pathways and their genetic links is the most important finding.

"When you delineate a pathway, you bring up new potential targets for therapy," he said. "The more targets you have, you open up the potential for having multiple drugs and attacking a cancer more easily, without it becoming more resistant."

Overall, Melner added, the results underscore the complexity of the different mechanisms involved in breast cancer development.

More information

For more about the genetics of breast cancer, visit the American Cancer Society.

SOURCES: Douglas Easton, Ph.D., professor, genetic epidemiology, University of Cambridge, England; Michael H. Melner, Ph.D., scientific program director, American Cancer Society; Jan. 22, 2012, Nature Genetics, online


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