Hemminki K et al. - In a report discussing the newly identified repertoire of cancer susceptibility genes and loci that are characterized by common risk alleles and low relative risks, it seems that in spite of the reservations for combining data on population attributable fraction (PAF) across populations, that the published first-generation genome-wide scans on breast, prostate and colorectal cancers have made successful inroads into genomics of common cancers, yet leaving the mechanisms to be explained Methods
Recent large genotyping studies have identified a new repertoire of cancer susceptibility genes and loci that are characterized by common risk alleles and low relative risks
Because of these properties, these loci explain a much larger proportion of the etiology of the particular cancers, described by the population attributable fraction (PAF), than of their familial risks (FRRs)
Results
For breast cancer, 9 established loci gave a joint PAF of >60%, but explaining only some 8% of the empirical FRR
For prostate cancer, 6 independent loci at chromosome 8q conferred a joint PAF of 35% but the loci explained no more than 1.9% of the empirical excess familial risks
For colorectal cancer, the contributions of the 2 identified loci to PAF and FRR were somewhat lower
The genome-wide array platforms have been built for common variants, constraining the results to variants with high PAFs and low FRRs
Common variants are likely to tag rarer causative variants with much higher FRRs
Detected loci are noncoding and the underlying genetic mechanisms have not been worked out
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