New gene mutation, in PALB2, is linked to heightened breast cancer risk

August 8, 2014 | by

Twenty years ago, scientists discovered that a mutation in a gene now widely known as BRCA1 was linked to a sharply increased risk of breast cancer, paving the way for a new chapter in identifying women at risk of the disease and giving them options to potentially avoid an aggressive cancer. But experts have also long known that other genes probably play a role as well. Now, one of those genes has been identified: PALB2.

A new study links a mutation in the PALB2 gene to a higher risk of developing breast cancer.

BRCA1 and BRCA2 mutations are not alone in increasing breast cancer risk. A new study also links a mutation in the PALB2 gene to a higher risk of developing breast cancer.

Mutations in this gene, rarer than the BRCA1 and BRCA2 mutations, can make breast cancer nine times more likely to develop in women and eight times more likely for men, according to a study published this week in the New England Journal of Medicine from an international team of researchers, including two City of Hope scientists.

“This one is serious,” Jeffrey Weitzel, M.D., director of the Division of Clinical Cancer Genetics at City of Hope and one of the leaders of the study, told the Associated Press. Susan Neuhausen, Ph.D., The Morris & Horowitz Families Professor in Cancer Etiology and Outcomes Research, is also one of the study’s authors.

Weitzel said the gene is probably the most dangerous in terms of breast cancer risk after the BRCA genes. 

The study involved 362 members of 154 families with PALB2 mutations, and is the largest study of its kind. Mutations in the gene give women a 48 percent chance of developing breast cancer by age 70. The risk is greater for women with two or more close relatives with breast cancer.

The PALB2 gene – when it is not mutated – acts as a tumor suppressor along with BRCA2. When the gene is faulty, cancer can flourish. The mutation has been found in up to 4 percent of families with breast cancer history. No one is sure how common the gene mutation is, but Weitzel said he suspects it is more common than believed, simply because it has rarely been included in screening. He added that he has identified three cases among his patients in the last month.

Testing for this gene is available, and is often included in more comprehensive genetic testing. The new study offers clinicians and patients a better understanding of the risk associated with a mutation in the gene. Like people who are positive for other gene mutations, patients with the PALB2 mutation should be offered genetic counseling and may want to consider more frequent breast cancer screening, or other prophylactic options that can range from hormone-blocking pills to surgery.

Not everyone needs to be tested for genetic mutations linked to cancer risk. Those who are likely candidates for screening include people with a personal or family history of breast cancer; a personal or family history of male breast cancer, a personal or family history of ovarian cancer, or a close relative diagnosed with breast cancer before age 45. Women concerned about their breast cancer risk should speak with their doctors.

Weitzel has done considerable research in the field of breast cancer genetics, including developing an affordable testing panel for cancer risk screening and assisting in developing genetic testing programs in other countries.

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Learn more about breast cancer research and treatment at City of Hope. 

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