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GWAS Yields New Pancreatic Cancer Risk Loci

NEW YORK (GenomeWeb) – A study published online today in Nature Genetics has linked common variants at four loci to enhanced risk of pancreatic cancer.

An international team led by investigators at the Johns Hopkins School of Medicine conducted a two-stage genome-wide association study involving tens of thousands of individuals with or without pancreatic cancer. The search led to new and known pancreatic cancer risk loci, including SNPs on chromosomes 3, 7, and 17 and a chromosome 2 locus previously implicated in disease risk in Han Chinese individuals.

"We have identified several new regions involved in pancreatic cancer susceptibility and provide additional evidence to support many of the established associations," senior author Alison Klein, an oncology and pathology researcher at Johns Hopkins, and her colleagues wrote, arguing that the study "highlights the importance of common variation in pancreatic cancer risk."

Using genotyping data for 4,164 individuals of European ancestry with pancreatic cancer and 3,792 unaffected controls enrolled from the same population — all enrolled through studies done by the Pancreatic Cancer Case-Control Consortium (PanC4) — the researchers initially narrowed in on loci previously associated with pancreatic cancer.

They also detected a risky region on chromosome 17 that fell in and around LINC00673, which codes for a long, intergenic, non-coding RNA.

Another SNP at the same chromosome 17 locus turned up when the team did a genome-wide meta-analysis of the PanC4 data in conjunction with directly tested and imputed genotyping profiles for almost 3,500 cases and close to 3,600 controls who were enrolled for past GWAS known as PanScan 1 and PanScan 2.

The combined analysis also unearthed pancreatic cancer-associated variants at a chromosome 3 locus near the TP63 gene.

Through replication and combination testing that included genotyping information on another 2,497 individuals with pancreatic cancer and 4,611 without, the researchers narrowed in on two more new risk sites: one in the intron of a gene called SUGCT on chromosome 7 and another in the vicinity of the ETAA1 gene on chromosome 2.

The latter locus showed tenuous ties to pancreatic cancer in a past GWAS of individuals from the Han Chinese population, Klein and her co-authors noted.

Likewise, the team tracked down some genomic sites with modest pancreatic cancer associations, including a set of SNPs on chromosome 9 near the "structural maintenance of chromosome 2"-coding gene, SMC2, that only showed relationships to disease risk in the PanC4 cohort.

The study's authors noted that further follow-up research is needed to not only get a more complete picture of the genetic factors conferring increased pancreatic cancer risk, but also to delve into the functions of the common risk variants found so far.