New research has discovered that women in Iceland with a particular gene that raises the risk of breast cancer were virtually certain to develop the disease if they also had a mutation in another gene.
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.