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.
