Pancreatic cancer, a complex disease, emerges as a severe health problem worldwide and it exhibits a poor prognosis and high mortality. Risk factors associated with sporadic pancreatic cancer remain poorly understood, even less is known about disease prognosis due to its rapid progression. The PANcreatic Disease ReseArch (PANDoRA) consortium, of which the authors are members, was established to coordinate the efforts of different research groups to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. PANDoRA consortium has contributed to the identification of several low-penetrance risk loci for the disease both by candidate variants approach and genome-wide association studies, including those in cell-cycle and DNA damage response, telomere homeostasis, SCL and ABC transporters, ABO locus variability, mitochondrial metabolism and it participated on collaborative genome-wide association study approach and implementation of a search for functional-based pancreatic cancer risk loci and long noncoding RNAs. Complex studies covering genetic, environmental and microenvironmental factors in the pancreatic cancer onset, progression and its prognosis are warranted.

3rd Faculty of Medicine Charles University Prague Czech Republic

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Zobrazit více v PubMed

Gco.iarc.fr [Internet]. Cancer today. 2020 [Accessed 1 March 2022]. Available from: https://gco.iarc.fr/today/fact-sheets-cancers.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67:7–30. PubMed

Oldfield LE, Connor AA, Gallinger S. Molecular events in the natural history of pancreatic cancer. Trends Cancer 2017;3:336–46. PubMed

Gentiluomo M, Canzian F, Nicolini A, Gemignani F, Landi S, Campa D. Germline genetic variability in pancreatic cancer risk and prognosis. Semin Cancer Biol 2022;79:105–31. PubMed

Campa D, Rizzato C, Capurso G, Giese N, Funel N, Greenhalf W, et al. . Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium. Dig Liv Dis 2013;45:95–9. PubMed

Naccarati A, Pardini B, Polakova V, Smerhovsky Z, Vodickova L, Soucek P, et al. . Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: An association study in the Czech Republic. Carcinogenesis 2010;31:666–70. PubMed

Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, et al. . Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 2018;319:2401–9. PubMed PMC

Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, et al. . Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009;41:986–90. PubMed PMC

Rizzato C, Campa D, Pezzilli R, Soucek P, Greenhalf W, Capurso G, et al. . ABO blood groups and pancreatic cancer risk and survival: results from the PANcreatic Disease ReseArch (PANDoRA) consortium. Oncol Rep 2013;29:1637–44. PubMed

Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, et al. . A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 2010;42:224–8. PubMed PMC

Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, et al. . Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet 2015;47:911–6. PubMed PMC

Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, et al. . TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer 2015;137:2175–83. PubMed PMC

Antwi SO, Bamlet WR, Broderick BT, Chaffee KG, Oberg A, Jatoi A, et al. . Genetically predicted telomere length is not associated with pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 2017;26:971–4. PubMed PMC

Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J, et al. . Association between telomere length and risk of cancer and non-neoplastic diseases: a mendelian randomization study. JAMA Oncol 2017;3:636–51. PubMed PMC

Kroupa M, Rachakonda SK, Liska V, Srinivas N, Urbanova M, Jiraskova K, et al. . Relationship of telomere length in colorectal cancer patients with cancer phenotype and patient prognosis. Br J Cancer 2019;121:344–50; PubMed PMC

Kroupa M, Rachakonda S, Vymetalkova V, Tomasova K, Liska V, Vodenkova, et al. . Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients. Mutagenesis 2020;35:491–7. PubMed

Campa D, Pastore M, Gentiluomo M, Talar-Wojnarowska R, Kupcinskas J, Malecka-Panas E, et al. . Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. Oncotarget 2016;7:57011–20. PubMed PMC

Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, et al. . Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. Oncotarget 2016;7:66328–43. PubMed PMC

Mohelnikova-Duchonova B, Strouhal O, Hughes DJ, Holcatova I, Oliverius M, Kala Z, et al. . SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. Sci Rep 2017;7:43812. PubMed PMC

Campa D, Pastore M, Capurso G, Hackert T, Di Leo M, Izbicki JR, et al. . Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. Int J Cancer 2018;142:290–6. PubMed

Campa D, Matarazzi M, Greenhalf W, Bijlsma M, Saum KU, Pasquali C, et al. . Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study. Int J Cancer 2019;144:1275–83. PubMed

Obazee O, Archibugi L, Andriulli A, Soucek P, Małecka-Panas E, Ivanauskas A, et al. . Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma. Int J Cancer 2019;145:686–93. PubMed

Campa D, Gentiluomo M, Obazee O, Ballerini A, Vodickova L, Hegyi P, et al. . Genome-wide association study identifies an early onset pancreatic cancer risk locus. Int J Cancer 2020;147:2065–74. PubMed

Peduzzi G, Gentiluomo M, Tavano F, Arcidiacono PG, Ermini S, Vodicka P, et al. . Genetic polymorphisms involved in mitochondrial metabolism and pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 2021;30:2342–5. PubMed

Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, et al. . Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 2014;46:994–1000. PubMed PMC

Klein A, Wolpin BM, Risch HA, Stolzenberg-Solomon RZ, Mocci E, Zhang M, et al. . Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat Commun 2018;9:556. PubMed PMC

Galeotti AA, Gentiluomo M, Rizzato C, Obazee O, Neoptolemos JP, Pasquali C, et al. . Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction. J Med Genet 2021;58:369–77. PubMed

Lu Y, Corradi C, Gentiluomo M, López de Maturana E, Theodoropoulos GE, Roth S, et al. . Association of genetic variants affecting microRNAs and pancreatic cancer risk. Front Genet 2021;12:693933. PubMed PMC

Pistoni L, Gentiluomo M, Lu Y, López de Maturana E, Hlavac V, Vanella G, et al. . Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma. Carcinogenesis 2021;42:1037–45. PubMed

Corradi C, Gentiluomo M, Gajdán L, Cavestro GM, Kreivenaite E, Di Franco G, et al. ., Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility. Int J Cancer 2021;148:2779–88. PubMed

Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, et al. . A transcriptome-wide association study identifies novel candidate susceptibility genes for pancreatic cancer. J Natl Cancer Inst 2020;112:1003–12. PubMed PMC

Gentiluomo M, Puchalt García P, Galeotti AA, Talar-Wojnarowska R, Tjaden C, Tavano F, et al. . Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. Carcinogenesis 2019;40:544–50. PubMed

Gentiluomo M, Corradi C, Vanella G, Johansen AZ, Strobel O, Szentesi A, et al. . Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival. Sci Rep 2021;11:7570. PubMed PMC

Wang X, Ren H, Zhao T, Ma W, Dong J, Zhang S, et al. . Single nucleotide polymorphism in the microRNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes. Oncotarget 2016;7:13717–29. PubMed PMC

Lin Y, Nakatochi M, Hosono Y, Ito H, Kamatani Y, Inoko A, et al. . Genome-wide association meta -analysis identifies GP2 gene risk variants for pancreatic cancer. Nat Commun 2020;11:3175. PubMed PMC

Daoud AZ, Mulholland EJ, Cole G, McCarthy HO., MicroRNAs in pancreatic cancer: biomarkers, prognostic, and therapeutic modulators. BMC Cancer 2019;19:1130. PubMed PMC

Bunduc S, Gede N, Váncsa S,Lillik V, Kiss S, Dembrovszky F, et al. . Prognostic role of cell-free DNA biomarkers in pancreatic adenocarcinoma: a systematic review and meta–analysis. Crit Rev Oncol Hematol 2022;169:103548. PubMed

Cervena K, Vodicka P, Vymetalkova V. Diagnostic and prognostic impact of cell-free DNA in human cancers: systematic review. Mutat Res Rev Mutat Res 2019;781:100–29. PubMed

Principe DR, Rana A. Updated risk factors to inform early pancreatic cancer screening and identify high risk patients. Cancer Lett 2020;485:56–65. PubMed PMC

Commentary: Special Issue: Current Understanding of Colorectal and Pancreatic Cancers