Correlated regions of systemic interindividual variation (CoRSIV) represent a small
proportion of the human genome showing DNA methylation patterns that are the same
in all human tissues, are different among individuals, and are partially regulated
by genetic variants in cis. In this study we aimed at investigating single-nucleotide
polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma
(PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases
and 247,022 controls of European and Asian descent. We observed that the A allele
of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81
× 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage
disequilibrium with a variant (rs2294008) that has been reported to be associated
with risk of many other cancer types. The A allele is associated with the DNA methylation
level of the gene according to the PanCan-meQTL database and with overexpression according
to QTLbase. The expression of the gene has been observed to be deregulated in many
tumors of the gastrointestinal tract including pancreatic cancer; however, functional
studies are needed to elucidate the function relevance of the association.
