New genetic clue discovered about breast cancer

October 22, 2015

A specific variant of a gene called BARD1 appears to raise the risk of a woman developing breast cancer by a significant amount.

Two genes discovered a decade ago, BRCA1 and BRCA2, have been linked to hereditary forms of breast cancer and women with either one of them have 3 to 7 times the risk of developing the disease compared with women who lack such genes.

But they account for only 10 percent to 15 percent of total breast cancer cases, and not most of the inherited ones, so scientists have been searching for other genes that may act alone or with them to raise the risk.

One in eight women will develop breast cancer during their lifetime, depending on a range of factors such as whether she has had children and at what age, when she started and stopped her periods, and her exposure to certain chemicals or radiation.

Some women may also have inherited a defective gene that affects her risk of developing breast cancer and up to 10% of all breast cancers are familial, or inherited.

In 20% of these cases, the gene that is defective is BRCA1 or BRCA2 and inheriting a defective copy of one of these genes greatly increases a woman's risk of developing breast cancer.

Researchers suspect that there are other inherited genes that predispose to breast cancer which have yet to be identified but they are believed to have a much weaker effect and are described as low-penetrance genes.

Inheriting one such gene only slightly increases breast cancer risk and a woman has to inherit several to increase her lifetime risk of cancer significantly.

In order to find low-penetrance genes, researchers need a large group of women with breast cancer and a similar group of women without cancer, in order to examine how often a specific gene variant occurs in the two groups.

If the variant is found more often in the cases than in the controls, it might be a variant that increases a woman's risk of developing breast cancer.

For this study the researchers led by Dr. Kari Stefansson and colleagues at deCode genetics Inc. in Reykjavik, Iceland, studied 1,090 Icelandic women who had had breast cancer and 703 unaffected women, and looked for a specific variant (Cys557Ser allele) of a gene called BARD1.

BARD1 was chosen because the protein it encodes interacts with the protein encoded by BRCA1 and as defects in BRCA1 increase the risk of breast cancer, defects in an interacting protein might have a similar effect which has been implicated in breast cancer in other studies.

A specific BARD1 mutation was found in 2.8 percent of women with cancer but only 1.6 percent of women without it.

More surprisingly, the risk of developing breast cancer roughly doubled for women with the BARD1 mutation and the BRCA2 mutation most common in Iceland.

Stefansson says together the two predict a certainty of breast cancer.

In the United States, BRCA1 is more common than BRCA2, especially among Ashkenazi Jewish women and many women with the bad genes face agonizing decisions over whether to have mastectomies or subject themselves to preventive therapies.

Researchers believe if the role of BARD1 is confirmed in breast cancer, women will be able to make better decisions.

Breast cancer is the most common major cancer in women and the second leading cause of cancer deaths in women; as many as 213,000 new cases are expected to occur in the United States this year and more than 1 million worldwide.

The study was published by the online science journal PLoS Medicine.