Although genome-wide association studies have led to the
identification of genetic risk factors for colorectal, prostate, testicular and
thyroid cancers, researchers from Greece suggest their small sample size limit
their predictive power.
Performing genome-wide association studies using
all currently available samples on common cancers would yield many more genetic
loci, but almost all of them would also have small or very small effects,
the researchers wrote.
For this review, the researchers pooled data from 56
genome-wide association studies published from 2007 to 2010. The data were
assessed with 25,000 persons per cancer type to identify the sample size needed
to detect associations between these alleles and the risk for colorectal,
prostate, testicular and thyroid cancers.
The following questions were addressed:
- Is the pace of new discoveries of associations between common variants
and cancer accelerating or decelerating?
- How strong is the magnitude of the discovered effects in terms of the
genetic risk conferred and the frequency of the risk variants?
- How extensive might the discrimination of risk be if information from
all identified risk variants is used?
- Is the pattern of discovered effects reflective primarily of statistical
power considerations and would it be possible to find many more similar
associations if larger studies could be performed with the same platforms?
Ninety-two associations were eligible for evaluation
more than half involved prostate (n=27, 26 independent loci), colorectal
(n=11, 10 loci), and breast cancers (n=11 loci). Eighty-one were independently
Further, an exponential correlation was identified
between the increased rate for discovery with 15 occurring during 2007, 25
during 2008, 50 during 2009, and two during 2010. Moreover, 69 associations
were of European descent; 16 of both European and other populations; and seven
of Asian descent.
Clearly, statistically well-powered genome-wide
association studies are needed to address gene-gene and gene-environment
interactions, David J. Hunter, MD, of the Program in Molecular and
Genetic Epidemiology at the Harvard School of Public Health, and Stephen
Chanock, MD, of the division of cancer epidemiology and genetics, at the
NCI wrote in an accompanying editorial. The coming years promise to be an
exciting time for the genetic epidemiology of cancer, even if they have more of
a taste of consolidation, rather than the revolutionary flavor of the past
Ioannidis JPA. J Natl Cancer Inst.
Hunter DJ. J Natl Cancer Inst. 2010;102.
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