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 single
letter variations (SNPs) on chromosome 17 associated with
increased risk of prostate cancer. Intriguingly, one of the
variants is also associated with decrease in risk of type
2 diabetes (T2D). The increase in risk of prostate cancer
conferred by these variants is relatively modest: between
20 and 30% per copy carried compared to individuals without
the variants.
But because
these variants are very common, they are estimated to play
a role in more than a third of prostate cancer cases. The
study included some 3,500 prostate cancer patients and more
than 14,000 controls from Iceland, Spain, the Netherlands
and the U.S. The paper, entitled “Two variants on chromosome
17 confer prostate cancer risk, and the one in TCF2 protects
against type 2 diabetes,” is published online today Nature
Genetics at www.nature.com/ng and is scheduled to appear
in the August print edition of the journal.
Adding these new variants to those previously discovered
by deCODE on chromosome 8q24, the company now has a collection
of genetic factors with sufficient impact on individual risk
of prostate cancer to develop a DNA-based risk screening
test. Such a test could be used to identify individuals who
should receive frequent screening.
deCODE has recently published the identification of two
variants on chromosome 8q24 linked to increased risk of prostate
cancer, the only two variants to emerge with genome-wide
significance from the first-pass analysis of more than 300,000
SNPs captured by the Illumina Hap300 bead arrays. However
it was clear that major variants influencing the risk of
prostate cancer remained unidentified, so the deCODE team
followed up on previously reported family-based linkage signals
on the long arm of chromosome 17. By genotyping additional
markers in this region in case-control cohorts from Iceland,
Spain, the Netherlands and the U.S., the deCODE team discovered
and replicated two new SNPs conferring risk of prostate cancer:
rs4430796 within the TCF2 gene on chromosome 17q12 previously
identified as a candidate gene in T2D; and rs1859962 on 17q24.
Previous epidemiological studies have uncovered an inverse
relationship between the incidence of prostate cancer and
type 2 diabetes (T2D). The deCODE team therefore decided
to investigate whether the risk variant in the TCF2 gene
might correlate with decreased likelihood of T2D. In a case-control
T2D cohort in Iceland, the risk allele of rs4430796 was found
to confer an approximately 10% decrease in the likelihood
of T2D, a result that was confirmed in seven additional case
control T2D cohorts in individuals of European, African and
Asian ancestry.
