Genome-wide association studies on risk and survival of pancreatic cancers

Pancreatic cancer is a leading cause of cancer deaths, with a five-year survival of barely 10%, particularly for pancreatic ductal adenocarcinoma (PDAC), the most common form.
Established risk factors include cigarette smoking, obesity, diabetes type II, pancreatitis and family history of pancreatic cancer. Genome-wide association studies (GWAS), to which we contributed, have recently identified about 30 genetic loci affecting PDAC risk (PMID: 19648918, 20101243, 25086665, 26098869, 27579533, 29422604).
We established the international PANcreatic Disease ReseArch (PANDoRA) consortium (PMID: 23206934) to study genetic susceptibility to pancreatic cancer. PANDoRA is based in various European countries, in addition to Japan and Brazil. We collected DNA samples and data of over 4,000 PDAC cases and 5,000 healthy controls, and smaller numbers of other pancreatic tumors (in particular about 800 cases of pancreatic neuroendocrine tumors (PNET)), precursors of PDAC (about 1000 cases of intraductal papillary mucinous neoplasm (IPMN)) and chronic pancreatitis (about 1200 cases), making PANDoRA one of the leading resources worldwide.
We used PANDoRA to contribute to the above mentioned GWAS, to perform candidate gene studies, as well as secondary analyses using publicly available GWAS data and PANDoRA (PMID: 32818625, 32591343, 33534179, 33879152, 34216462, 34527018, 34526302, 34926279, 36302831, 35472852, and manuscripts submitted / in preparation).
A new, larger GWAS on PDAC risk, named PanScan4, is currently ongoing, with coordination by the National Cancer Institute in the USA (Dr. L. Amundadottir). We contributed a large number of PDAC cases and controls from PANDoRA, which have been genotyped with a SNP array (Illumina Global Screening Array). Our data will be meta-analyzed with those of other consortia, for an expected final sample size of about 25,000 PDAC cases and a similar number of controls of European ancestry.
In addition, we have also scanned available PANDoRA cases of PNET and IPMN, with the aim of performing GWASs for risk of those entities as well. Additional PANDoRA PNET and IPMN cases are in the process of being genotyped. We will use the PANDoRA controls previously genotyped in the context of PanScan4 for the PNET and IPMN GWASs as well.
Two Dutch centers (Amsterdam Medical Centre (Prof. O. Busch) and Rotterdam Erasmus Medical Centre (Prof. C.H.J. van Eijck)) participate in PANDoRA, and have thus far provided biological samples and data of slightly over 200 cases of pancreatic cancers and precursors (PDAC, PNET and IPMN). Recruitment of new cases by our Dutch clinical collaborators is ongoing, therefore the number of available samples is expected to increase in the future. Thus far we have used Dutch controls from the EPIC cohort (https://epic.iarc.fr). However, only about 100 controls from EPIC-Netherlands with genome-wide SNP genotyping are available. This number is insufficient to match the ~200 Dutch pancreatic cancer cases currently available, and this problem will become even worse when more Dutch pancreatic cancer patients are recruited into PANDoRA. We need therefore an alternative set of controls of sufficient size.