Genome-wide association studies require larger cohort size

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 associated.

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 three years.”

Ioannidis JPA. J Natl Cancer Inst. 2010;102:1–13.

Hunter DJ. J Natl Cancer Inst. 2010;102.