In a paper published today, a team of scientists from deCODE genetics (Nasdaq:DCGN) and academic colleagues from Europe and the United States report the discovery of two novel and very common genetic variants linked to susceptibility to breast cancer. The variants are single-letter variations in the sequence of the genome, or SNPs, located on chromosome 2 and chromosome 16, and each independently confers increased risk of breast cancer in women of European descent.
Most previously known genetic risk factors for breast cancer, like those in the BRCA1 and BRCA2 genes, confer strongly increased risk of the disease but are quite rare, and therefore account for only a small proportion of inherited breast cancer risk in the general population. The variants reported today are among the first common, replicated genetic risk factors for the disease. They confer a relatively modest increase in risk, but because they are inherited by a large proportion of women, their public health impact is substantial. The deCODE-led team reports that 25% of women of European descent women carry two copies of the risk variant on chromosome 2, corresponding to an approximately 44% increase in risk of the disease compared to those with no copies of the variant. Around 7% of women of European origin have inherited two copies of the risk variant on chromosome 16, corresponding to a 64% increase in risk when compared to that of non-carriers.
deCODE estimates that these two variants are contributing factors in one quarter of breast cancer cases in women of European origin. deCODE plans to use these discoveries as the starting point for the development of DNA-based tests which might identify women who would benefit from more intensive breast cancer screening and prevention measures. Such tests will incorporate other common variants as they are discovered, as well as information on the impact of these variants in women from around the world. deCODE is initiating studies to evaluate how well these tests might be intergrated into current practice in breast cancer screening, prevention and therapy.
The paper, entitled “Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer,” is published today in the online edition of Nature Genetics, and will appear in an upcoming print edition of the journal.
The first step in these discoveries was a genome-wide association study that looked at more than 300,000 SNP markers in a large group of Icelandic breast cancer patients and healthy control subjects. Several SNPs that showed an association with the disease were then tested in other case-control groups from Iceland, Sweden, Spain, The Netherlands and the United States; version A of SNP rs13387042 on chromosome 2q35 and version T of rs3803662 on chromosome 16q12 showing significant association with the disease in all cohorts of European origin studied. More detailed examination of the subtypes of breast cancer among patients in the study showed that these variants were associated predominantly with estrogen receptor positive tumors.
The region surrounding the variant on chromosome 2 harbors no known genes, so the mechanism by which it impacts risk reamians to be elucidated. The variant on chromosome 16 is very close to a gene called TNRC9 which has been linked in previous studies to the metastasis, or spread, of breast cancer to the bones.