PANDoRA

Several studies focusing on the association between single nucleotide polymorphisms (SNPs) and pancreatic cancer risk and/or survival have already been successfully performed in the context of the PANDoRA consortium:

Title: Replication of PanScan findings
PI(s): Cosmeri Rizzato, Daniele Campa, Federico Canzian.
Institution(s): Genomic Epidemiology Group, DKFZ.
Description: We analyzed a total of 19 genetic variants in the SHH, ABO, TERT, NR5A2 regions and in the two gene deserts on chromosome 13 and 15, on 690 PDAC cases and 1277 controls.
Results: We were able to replicate almost all the associations found by PanScan. Moreover, one of the SNPs on chromosome 15 showed an association with survival of pancreatic cancer patients.
Paper: Rizzato, Campa et al, PLoS One 2011.

Title: Genetic variability of the ABO locus and its role in PDAC risk and survival
PI(s): Cosmeri Rizzato, Daniele Campa, Federico Canzian.
Institution(s): Genomic Epidemiology Group, DKFZ.
Description: We analyzed in depth SNPs covering the ABO locus.
Results: We found that the ABO locus is indeed associated with increased risk of pancreatic cancer, but it does not affect patients survival.
Paper: Rizzato, Campa et al, Oncol Rep 2013.

Title: Replication of loci from Asian GWAS
PI(s): Daniele Campa Cosmeri Rizzato, Federico Canzian.
Institution(s): Genomic Epidemiology Group, DKFZ.
Description: We attempted to replicate the eight novel loci discovered in the Chinese and Japanese GWAS.
Results: None of seven SNPs we genotyped (one more SNP is polymorphic in Asians but not in Europeans) were convincingly associated with PDAC risk in individuals of European descent.
Paper: Campa, Rizzato et al, Cancer Epidemiol Biomarkers Prev 2013.

Title: PanScan3 GWAS
PI(s): Cosmeri Rizzato, Daniele Campa, Federico Canzian, in collaboration with PanScan investigators
Institution(s): Genomic Epidemiology Group, DKFZ.
Description: The PANDoRA Consortium has participated in PanScan3, a GWAS on PDAC in close collaboration with the National Cancer Institute of the USA (NCI). A part of the PANDoRA samples (around 200 cases) have been genotyped by the Illumina Human OmniExpress 770-Quad chip, while the rest of the cases and controls have been used as the primary replication set of the project.
Results: A number of novel risk loci have been identified.
Paper: Wolpin, Rizzato et al, Nat Genet 2014.

Title: PanC4 GWAS
PI(s): Daniele Campa, Cosmeri Rizzato, Federico Canzian, in collaboration with PanC4 investigators
Institution(s): Genomic Epidemiology Group, DKFZ.
Description: A further GWAS has been performed, in collaboration with the PanC4 consortium. In this case, again, PANDoRA has been used as replication set of the project.
Results: This work has yielded several additional novel risk loci.
Paper: Childs, Mocci, Campa et al, Nat Genet 2015.
 

Title: Genetic variability at TERT/TERC

PI(s): Daniele Campa Cosmeri Rizzato, Federico Canzian.

Institution(s): Genomic Epidemiology Group, DKFZ.

Description: We genotyped in depth the TERT and TERC loci. We selected 28 tagging and functional SNPs, in order to replicate and expand the findings of the PanScan GWAS.

Results: We identifed an additional susceptibility SNP at the TERT locus, independent from PanScan findings.

Paper: Campa, Rizzato et al, Int J Cancer 2015.

 

Title: Replication of findings of survival GWAS

PI(s): Cosmeri Rizzato, Daniele Campa, Federico Canzian.

Institution(s): Genomic Epidemiology Group, DKFZ.

Description: We genotyped in PANDoRA the best associations of the recently performed GWAS on PDAC survival (Wu et al 2014).

Results: We could replicate a small number of associations.

Paper: Rizzato, Campa et al, Carcinogenesis 2016.

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Title: Imputation in PanScan GWAS

PI(s): Federico Canzian, in collaboration with PanScan investigators

Institution(s): Genomic Epidemiology Group, DKFZ.

Description: Following imputation of PanScan genotypes using reference data of the 1000 Genomes project (performed at NCI), additional candidate SNPs were tested on PANDoRA cases and controls.

Results: Three additional independent risk SNPs were found at the TERT-CLPTM1L, NR5A2 and 8q24 loci.

Paper: Zhang et al, Oncotarget 2016.

 

Title: SNPs of the p16 locus and PDAC risk

PI(s): Daniele Campa, Federico Canzian.

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: The CDKN2A/2B (p16/p15) region is particularly important for cancer susceptibility because it is considered a Nexus region (Chung and Chanock, 2011), i.e. a region that has been associated with genetic risk of various cancer types beyond pancreas. We thoroughly studied the variability of region in PDAC cases and controls with tagging and functional SNPs.

Results: We found that the rs3217992 SNP was associated with an increased pancreatic cancer risk. This SNP has been reported to affect miRNA binding.

Paper: Campa et al, Oncotarget 2016.

 

Title: SNPs of the p16 locus and PNET risk

PI(s): Daniele Campa, Federico Canzian.

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: The CDKN2A/2B (p16/p15) region is particularly important for cancer susceptibility because it is considered a Nexus region (Chung and Chanock, 2011), i.e. a region that has been associated with genetic risk of various cancer types beyond pancreas. We thoroughly studied the variability of region in PNET cases and controls with tagging and functional SNPs.

Results: We observed an association between rs2518719 SNP and an increased risk of developing PNET.

Paper: Campa et al, Sci Rep 2016.

 

Title: Replication of loci associated with PNET from the literature

PI(s): Daniele Campa, Federico Canzian

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: We tried to validate the top SNPs reported in the literature to be associated with PNET risk (Ter-Minassian et al 2011).

Results: After correction for multiple testing, we did not observe any statistically significant association between the selected SNPs and PNET risk.

Paper: Campa et al, CEBP 2017.

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Title: SNPs of the SLC22A3 locus and PDAC risk

PI(s): Beatrice Mohelnikova-Duchonova, Pavel Soucek

Institution(s): National Institute of Public Health, Prague, Czech Republic

Description: The hypothesis, that SLC22A3 could be associated with pancreatic cancer and that SLC22A3 influences the prognosis of pancreatic cancer patients, was evaluated by the analysis of SNPs in SLC22A3 on pancreatic cancer samples and control group of PANDoRA sample set.

Results: No SNPs were associated with pancreatic cancer risk when multiple testing was accounted for, but one SNP was associated with survival of pancreatic cancer patients.

Paper: Mohelnikova-Duchonova et al, Sci Rep 2017.

 

Title: CP loci and PDAC risk

PI(s): Daniele Campa, Federico Canzian.

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: CP is a strong risk factor for pancreatic cancer and therefore one of the goals of PANDoRA is to explore the possibility that the two diseases share some risk factors. We genotyped GWAS-identified CP susceptibility loci (Whitcomb et al 2012) in all the CP and PDAC cases and healthy controls present in the PANDoRA consortium bio-bank in order to: 1) replicate the finding by Whitcomb and colleagues, 2) establish whether the SNPs associated with risk of CP are also PDAC susceptibility loci.

Results: All the SNPs confirmed statistically significant associations with CP risk. We found a weak association between one SNP and PDAC risk.

Paper: Campa et al, in press.

 

Title: Taste receptor SNPs and PDAC risk

PI(s): Daniele Campa Cosmeri Rizzato, Federico Canzian.

Institution(s): Genomic Epidemiology Group, DKFZ.

Description: We genotyped taste receptor genes (TAS2Rs), which are localized in two clusters on chromosomes 7 and 12. Taste receptor genes are expressed in the whole gastrointestinal tract (Behrens and Meyerhof 2010) and they have the function to react to bitter or sweet compounds. They are thought to have a very important role in eliminating toxic compounds in the organism. Moreover they are expressed in the pancreas and they regulate the release of gustacidin, which in turn regulates insulin secretion. Since obesity and type 2 diabetes are risk factors for pancreatic cancer, this is a promising group of genes to study.

Results: We did not find statistically significant associations between taste receptor gene SNPs and pancreatic cancer risk.

Paper: Gentiluomo et al, manuscript under review.

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Title: BRCA2 K3326X polymorphism and PDAC risk

PI(s): Ofure Obazee, Federico Canzian.

Institution(s): Genomic Epidemiology Group, DKFZ.

Description: The rare truncating BRCA2 K3326X (rs11571833) variant has previously been implicated in familial PDAC, but not sporadic cases. We genotyped it and the pathogenic frameshift BRCA2 deletion rs11571658, known to co-occur with rs11571833, in PANDoRA PDAC cases and controls.

Results: BRCA2 K3326X increases sporadic PDAC risk.

Paper: Obazee et al, manuscript under review.

 

Title: PDAC loci in PNET risk

PI(s): Ofure Obazee, Federico Canzian, Daniele Campa

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: We verified whether known genetic risk factors for PDAC emerging from GWAS are also associated with PNET susceptibility.

Results: We found weak assocations between two PDAC risk SNPs and PNET risk.

Paper: Obazee et al, manuscript under review.

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Title: Telomeric gene score to predict pancreatic cancer risk

PI(s): Daniele Campa, Federico Canzian

Institution(s): Dept. of Biology, University of Pisa, and Genomic Epidemiology Group, DKFZ.

Description: We genotyped 11 SNPs shown by GWAS to be associated with telomere length measured in leukocytes (LTL). We used the genotypes to compute a polygenic score ("teloscore") as a proxy for LTL and analyze the possible association between the score and pancreatic cancer risk.

Results: We found associations between two individual SNPs predicting LTL and PDAC risk, at genome-wide significance level. We also found a statistically significant association between the teloscore and PDAC risk.

Paper: Campa et al, manuscript under review.

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