In our application to endometrial cancer, there was an abundance of creQTLs in noncoding regions and introns, and relatively very few in coding regions. Polymorphisms in coding regions, although observed less frequently, would likely generate more pronounced effects, and for signaling molecules, these could result in substantial downstream effects important for carcinogenesis due to a change in function of the protein. However, these alleles, which are likely to be under strong negative selection and very rare, would not be covered by the genotyping platform used in the present study. Unlike the results of eQTL studies, our strongest hits were not typically located in cis regions very close to the coding sequences of individual genes, but rather in more distant, noncoding regions located over 10 KB from the nearest gene. This suggests that regions that regulate clusters of genes, unlike those regulating individual genes, are located farther from coding sequences and may possibly function as general enhancers. However, without careful experimentation, such as promoter reporter gene assays that would specifically test the enhancer activity of these sequences, it is difficult to
