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Another faulty gene can raise breast cancer risk nearly as much as BRCA genes do, study finds

It's long been known that faulty BRCA genes greatly raise the risk for breast cancer. Now scientists say a more recently identified, less common gene can do the same.

Mutations in the gene can make breast cancer up to nine times more likely to develop, an international team of researchers reports in this week's New England Journal of Medicine.

About 5 to 10 per cent of breast cancers are thought to be due to bad BRCA1 or BRCA2 genes. Beyond those, many other genes are thought to play a role but how much each one raises risk has not been known, said Dr. Jeffrey Weitzel, a genetics expert at City of Hope Cancer Center in Duarte, Calif.

The new study on the gene— called PALB2 — shows "this one is serious," and probably is the most dangerous in terms of breast cancer after the BRCA genes, said Weitzel, one of leaders of the study.

It involved 362 members of 154 families with PALB2 mutations — the largest study of its kind. The faulty gene seems to give a woman a 14 per cent chance of breast cancer by age 50 and 35 per cent by age 70 and an even greater risk if she has two or more close relatives with the disease.

That's nearly as high as the risk from a faulty BRCA2 gene, Dr. Michele Evans of the National Institute on Aging and Dr. Dan Longo of the medical journal staff write in a commentary in the journal.

The PALB2 gene works with BRCA2 as a tumour suppressor, so when it is mutated, cancer can flourish.

How common the mutations are isn't well known, but it's "probably more than we thought because people just weren't testing for it," Weitzel said. He found three cases among his own breast cancer patients in the last month alone.

Among breast cancer patients, BRCA mutations are carried by 5 per cent of whites and 12 per cent of Eastern European (Ashkenazi) Jews. PALB2 mutations have been seen in up to 4 per cent of families with a history of breast cancer.

Men with a faulty PALB2 gene also have a risk for breast cancer that is eight times greater than men in the general population.

Testing for PALB2 often is included in more comprehensive genetic testing, and the new study should give people with the mutation better information on their risk, Weitzel said. Doctors say that people with faulty cancer genes should be offered genetic counselling and may want to consider more frequent screening and prevention options, which can range from hormone-blocking pills to breast removal.

The actress Angelina Jolie had her healthy breasts removed last year after learning she had a defective BRCA1 gene.

The study was funded by many government and cancer groups around the world and was led by Dr. Marc Tischkowitz of the University of Cambridge in England. The authors include Mary-Clare King, the University of Washington scientist who discovered the first breast cancer predisposition gene, BRCA1.

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Online:

Study: http://www.nejm.org/doi/full/10.1056/NEJMoa1400382

Gene info: http://ghr.nlm.nih.gov/gene/PALB2

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Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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