Current challenges and opportunities for chemoprevention of pancreatic cancer

Current Medicinal Chemistry

Volumn 25, Issue 22, 2018, Pages 2535-2544

  Mohammed, Altaf ^a,b   Janakiram, Naveena B ^a   Madka, Venkateshwar ^a   Li, Min ^a   Asch, Adam S ^a   Rao, Chinthalapally V ^a  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Chemoprevention; Drug; Early detection; Genetically engineered mouse models; Invasive carcinoma; Pancreatic cancer; Targets

Indexed keywords

3 [[5 (2,3 DICHLOROPHENYL) 1H TETRAZOL 1 YL]METHYL]PYRIDINE; ACETYLSALICYLIC ACID; ALPHA TOCOPHEROL; ANTINEOPLASTIC AGENT; ATORVASTATIN; CELECOXIB; DELTA TOCOTRIENOL; EFLORNITHINE; GEFITINIB; LICOFELONE; METFORMIN; MUC1 VACCINE; OMEGA 3 FATTY ACID; SIMVASTATIN; SULINDAC; TOCOPHEROL DERIVATIVE; UNCLASSIFIED DRUG; VACCINE; CYCLOOXYGENASE 2; EPIDERMAL GROWTH FACTOR RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE;

CANCER GROWTH; CHEMOPROPHYLAXIS; HUMAN; METASTASIS; NONHUMAN; PANCREAS CANCER; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DISEASE MODEL; METABOLISM; PANCREAS TUMOR; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; CHEMOPREVENTION; CYCLOOXYGENASE 2; DISEASE MODELS, ANIMAL; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; NEOPLASM METASTASIS; PANCREATIC NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 85029060591     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867324666170209104453     Document Type: Review

References (70)

1. Ferlay, J.; Soerjomataram, I.; Ervik, M.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Available from: http://globocan.iarc.fr GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Internet., Lyon, France, International Agency for Research on Cancer, 2014. [Accessed on 16/01/2015]
2. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
3. American Cancer Society. Cancer Facts and Figures. Atlanta, GA, 2016.
4. Mohammed, A.; Janakiram, N.B.; Lightfoot, S.; Gali, H.; Vibhudutta, A.; Rao, C.V. Early detection and prevention of pancreatic cancer: Use of genetically engineered mouse models and advanced imaging technologies. Curr. Med. Chem., 2012, 19(22), 3701-3713.
5. Mohammed, A.; Janakiram, N.B.; Pant, S.; Rao, C.V. Molecular targeted intervention for pancreatic cancer. Cancers (Basel), 2015, 7(3), 1499-1542.
6. Aguirre, A.J.; Bardeesy, N.; Sinha, M.; Lopez, L.; Tuveson, D.A.; Horner, J.; Redston, M.S.; DePinho, R.A. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev., 2003, 17(24), 3112-3126.
7. Bardeesy, N.; Aguirre, A.J.; Chu, G.C.; Cheng, K-H.; Lopez, L.V.; Hezel, A.F.; Feng, B.; Brennan, C.; Weissleder, R.; Mahmood, U.; Hanahan, D.; Redston, M.S.; Chin, L.; Depinho, R.A. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc. Natl. Acad. Sci. USA, 2006, 103(15), 5947-5952.
8. Gopinathan, A.; Tuveson, D.A. The use of GEM models for experimental cancer therapeutics. Dis. Model. Mech., 2008, 1(2-3), 83-86.
9. Guerra, C.; Schuhmacher, A.J.; Cañamero, M.; Grippo, P.J.; Verdaguer, L.; Pérez-Gallego, L.; Dubus, P.; Sandgren, E.P.; Barbacid, M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell, 2007, 11(3), 291-302.
10. Guerra, C.; Collado, M.; Navas, C.; Schuhmacher, A.J.; Hernández-Porras, I.; Cañamero, M.; Rodriguez-Justo, M.; Serrano, M.; Barbacid, M. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene- induced senescence. Cancer Cell, 2011, 19(6), 728-739.
11. Hingorani, S.R.; Petricoin, E.F.; Maitra, A.; Rajapakse, V.; King, C.; Jacobetz, M.A.; Ross, S.; Conrads, T.P.; Veenstra, T.D.; Hitt, B.A.; Kawaguchi, Y.; Johann, D.; Liotta, L.A.; Crawford, H.C.; Putt, M.E.; Jacks, T.; Wright, C.V.; Hruban, R.H.; Lowy, A.M.; Tuveson, D.A. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell, 2003, 4(6), 437-450.
12. Hingorani, S.R.; Wang, L.; Multani, A.S.; Combs, C.; Deramaudt, T.B.; Hruban, R.H.; Rustgi, A.K.; Chang, S.; Tuveson, D.A. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell, 2005, 7(5), 469-483.
13. Ijichi, H.; Chytil, A.; Gorska, A.E.; Aakre, M.E.; Fujitani, Y.; Fujitani, S.; Wright, C.V.E.; Moses, H.L. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas- specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev., 2006, 20(22), 3147-3160.
14. Izeradjene, K.; Combs, C.; Best, M.; Gopinathan, A.; Wagner, A.; Grady, W.M.; Deng, C-X.; Hruban, R.H.; Adsay, N.V.; Tuveson, D.A.; Hingorani, S.R. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell, 2007, 11(3), 229-243.
15. Morton, J.P.; Timpson, P.; Karim, S.A.; Ridgway, R.A.; Athineos, D.; Doyle, B.; Jamieson, N.B.; Oien, K.A.; Lowy, A.M.; Brunton, V.G.; Frame, M.C.; Evans, T.R.; Sansom, O.J. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 246-251.
16. Rowley, M.; Ohashi, A.; Mondal, G.; Mills, L.; Yang, L.; Zhang, L.; Sundsbak, R.; Shapiro, V.; Muders, M.H.; Smyrk, T.; Couch, F.J. Inactivation of Brca2 promotes Trp53-associated but inhibits KrasG12D-dependent pancreatic cancer development in mice. Gastroenterology, 2011, 140(4), 1303-1313.e1, 3.
17. Wilde, R.F.; Hruban, R.H.; Maitra, A.; Johan, G.; Offerhaus, A. Reporting precursors to invasive pancreatic cancer: pancreatic intraepithelial neoplasia, intraductal neoplasms and mucinous cystic neoplasm. Diagn. Histopathol., 2012, 18(1), 17-30.
18. Matthaei, H.; Schulick, R.D.; Hruban, R.H.; Maitra, A. Cystic precursors to invasive pancreatic cancer. Nat. Rev. Gastroenterol. Hepatol., 2011, 8(3), 141-150.
19. Distler, M.; Aust, D.; Weitz, J.; Pilarsky, C.; Grützmann, R. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN. BioMed Res. Int., 2014. article ID 474905, 11.
20. Canto, M.I. Strategies for screening for pancreatic adenocarcinoma in high-risk patients. Semin. Oncol., 2007, 34(4), 295-302.
21. Canto, M.I.; Goggins, M.; Yeo, C.J.; Griffin, C.; Axilbund, J.E.; Brune, K.; Ali, S.Z.; Jagannath, S.; Petersen, G.M.; Fishman, E.K.; Piantadosi, S.; Giardiello, F.M.; Hruban, R.H. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin. Gastroenterol. Hepatol., 2004, 2(7), 606-621.
22. Canto, M.I.; Hruban, R.H.; Fishman, E.K.; Kamel, I.R.; Schulick, R.; Zhang, Z.; Topazian, M.; Takahashi, N.; Fletcher, J.; Petersen, G.; Klein, A.P.; Axilbund, J.; Griffin, C.; Syngal, S.; Saltzman, J.R.; Mortele, K.J.; Lee, J.; Tamm, E.; Vikram, R.; Bhosale, P.; Margolis, D.; Farrell, J.; Goggins, M. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology, 2012, 142(4), 796-804.
23. Miller, M.S.; Allen, P.; Brentnall, T.A.; Goggins, M.; Hruban, R.H.; Petersen, G.M.; Rao, C.V.; Whitcomb, D.C.; Brand, R.E.; Chari, S.T.; Klein, A.P.; Lubman, D.M.; Rhim, A.D.; Simeone, D.M.; Wolpin, B.M.; Umar, A.; Srivastava, S.; Steele, V.E.; Rinaudo, J.A. Pancreatic cancer chemoprevention translational workshop: Meeting report. Pancreas, 2016, 45(8), 1080-1091.
24. Mohammed, A.; Janakiram, N.B.; Madka, V.; Brewer, M.; Ritchie, R.L.; Lightfoot, S.; Kumar, G.; Sadeghi, M.; Patlolla, J.M.; Yamada, H.Y.; Cruz-Monserrate, Z.; May, R.; Houchen, C.W.; Steele, V.E.; Rao, C.V. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression. Oncotarget, 2015, 6(17), 15524-15539.
25. Rao, C.V.; Janakiram, N.B.; Madka, V.; Devarkonda, V.; Brewer, M.; Biddick, L.; Lightfoot, S.; Steele, V.E.; Mohammed, A. Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma. Oncotarget., 2015, 20, 6(32), 33290-33305.
26. Mohammed, A.; Janakiram, N.B.; Li, Q.; Madka, V.; Ely, M.; Lightfoot, S.; Crawford, H.; Steele, V.E.; Rao, C.V. The epidermal growth factor receptor inhibitor gefitinib prevents the progression of pancreatic lesions to carcinoma in a conditional LSL-KrasG12D/+ transgenic mouse model. Cancer Prev. Res. (Phila.), 2010, 3(11), 1417-1426.
27. Rao, C.V.; Mohammed, A.; Janakiram, N.B.; Li, Q.; Ritchie, R.L.; Lightfoot, S.; Vibhudutta, A.; Steele, V.E. Inhibition of pancreatic intraepithelial neoplasia progression to carcinoma by nitric oxide-releasing aspirin in p48(Cre/+)-LSL-Kras(G12D/+) mice. Neoplasia, 2012, 14(9), 778-787.
28. Mohammed, A.; Qian, L.; Janakiram, N.B.; Lightfoot, S.; Steele, V.E.; Rao, C.V. Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice. Int. J. Cancer, 2012, 131(8), 1951-1962.
29. Mohammed, A.; Janakiram, N.B.; Brewer, M.; Ritchie, R.L.; Marya, A.; Lightfoot, S.; Steele, V.E.; Rao, C.V. Antidiabetic drug metformin prevents progression of pancreatic cancer by targeting in part cancer stem cells and mTOR signaling. Transl. Oncol., 2013, 6(6), 649-659.
30. Mohammed, A.; Janakiram, N.B.; Brewer, M.; Duff, A.; Lightfoot, S.; Brush, R.S.; Anderson, R.E.; Rao, C.V. Endogenous n-3 polyunsaturated fatty acids delay progression of pancreatic ductal adenocarcinoma in Fat-1-p48(Cre/+)- LSL-Kras(G12D/+) mice. Neoplasia, 2012, 14(12), 1249-1259.
31. Mohammed, A.; Janakiram, N.B.; Madka, V.; Ritchie, R.L.; Brewer, M.; Biddick, L.; Patlolla, J.M.; Sadeghi, M.; Lightfoot, S.; Steele, V.E.; Rao, C.V. Eflornithine (DFMO) prevents progression of pancreatic cancer by modulating ornithine decarboxylase signaling. Cancer Prev. Res. (Phila.), 2014, 7(12), 1198-1209.
32. Fendrich, V.; Chen, N.M.; Neef, M.; Waldmann, J.; Buchholz, M.; Feldmann, G.; Slater, E.P.; Maitra, A.; Bartsch, D.K. The angiotensin-I-converting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Gut, 2010, 59(5), 630-637.
33. Fendrich, V.; Sparn, M.; Lauth, M.; Knoop, R.; Plassmeier, L.; Bartsch, D.K.; Waldmann, J. Simvastatin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Pancreatology, 2013, 13(5), 502-507.
34. Liao, J.; Hwang, S.H.; Li, H.; Liu, J.Y.; Hammock, B.D.; Yang, G.Y. Inhibition of chronic pancreatitis and murine pancreatic intraepithelial neoplasia by a dual inhibitor of c- RAF and soluble epoxide hydrolase in LSL-KrasG¹²D/Pdx- 1-Cre mice. Anticancer Res., 2016, 36(1), 27-37.
35. Husain, K.; Centeno, B.A.; Chen, D.T.; Fulp, W.J.; Perez, M.; Zhang Lee, G.; Luetteke, N.; Hingorani, S.R.; Sebti, S.M.; Malafa, M.P. Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSLKrasG12D/+; Pdx-1-Cre mice by vitamin E d-tocotrienol. Carcinogenesis, 2013, 34(4), 858-863.
36. Bai, H.; Li, H.; Zhang, W.; Matkowskyj, K.A.; Liao, J.; Srivastava, S.K.; Yang, G.Y. Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice. Carcinogenesis, 2011, 32(11), 1689-1696.
37. Mohammed, A.; Janakiram, N.B.; Madka, V.; Pathuri, G.; Li, Q.; Ritchie, R.; Biddick, L.; Kutsche, H.; Zhang, Y.; Singh, A.; Gali, H.; Lightfoot, S.; Steele, V.E.; Suen, C.S.; Rao, C.V. Lack of chemopreventive effects of dietary P2×7R inhibitors against pancreatic cancer in p48Cre/+- LSL-KrasG12D/+ mice. Cancer Res., 2016, 76(14), 5255-5255.
38. Liao, J.; Chung, Y.T.; Yang, A.L.; Zhang, M.; Li, H.; Zhang, W.; Yan, L.; Yang, G.Y. Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSLKrasG12D- LSL-Trp53R172H-Pdx1-Cre mice. Mol. Carcinog., 2013, 52(9), 739-750.
39. Li, H.; Yang, A.L.; Chung, Y.T.; Zhang, W.; Liao, J.; Yang, G.Y. Sulindac inhibits pancreatic carcinogenesis in LSLKrasG12D- LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10). Carcinogenesis, 2013, 34(9), 2090-2098.
40. Liby, K.T.; Royce, D.B.; Risingsong, R.; Williams, C.R.; Maitra, A.; Hruban, R.H.; Sporn, M.B. Synthetic triterpenoids prolong survival in a transgenic mouse model of pancreatic cancer. Cancer Prev. Res. (Phila.), 2010, 3(11), 1427-1434.
41. Mukherjee, P.; Basu, G.D.; Tinder, T.L.; Subramani, D.B.; Bradley, J.M.; Arefayene, M.; Skaar, T.; De Petris, G. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J. Immunol., 2009, 182(1), 216-224.
42. Chugh, R.; Sangwan, V.; Patil, S.P.; Dudeja, V.; Dawra, R.K.; Banerjee, S.; Schumacher, R.J.; Blazar, B.R.; Georg, G.I.; Vickers, S.M.; Saluja, A.K. A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer. Sci. Transl. Med., 2012, 4(156), 156ra139.
43. Haas, M.; Laubender, R.P.; Stieber, P.; Holdenrieder, S.; Bruns, C.J.; Wilkowski, R.; Mansmann, U.; Heinemann, V.; Boeck, S. Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer. Tumour Biol., 2010, 31(4), 351-357.
44. Ho, J.J.; Siddiki, B.; Kim, Y.S. Association of sialyl- Lewis(a) and sialyl-Lewis(x) with MUC-1 apomucin ina pancreatic cancer cell line. Cancer Res., 1995, 55(16), 3659-3663.
45. Steinberg, W. The clinical utility of the CA 19-9 tumorassociated antigen. Am. J. Gastroenterol., 1990, 85(4), 350-355.
46. Andrén-Sandberg, A. CA 50 and CA 19-9 in serum as tumor markers for pancreatic cancer: A review of the literature. Acta Chir. Scand. Suppl., 1989, 549, 75-81.
47. Hosokawa, Y.; Nagakawa, Y.; Sahara, Y.; Takishita, C.; Katsumata, K.; Tsuchida, A. Serum SPan-1 is a significant risk factor for early recurrence of pancreatic cancer after curative resection. Dig. Surg., 2017, 34(2), 125-132.
48. Kokhanenko, N.Iu.; Ignashov, A.M.; Varga, E.V.; Polkanova, M.S.; Aleshina, L.A.; Kimbarovskaia, A.A.; Osipenko, S.K.; Lebedev, E.G. [Role of the tumor markers CA 19-9 and carcinoembryonic antigen (CEA) in diagnosis, treatment and prognosis of pancreatic cancer]. Vopr. Onkol., 2001, 47(3), 294-297.
49. Baeckström, D.; Hansson, G.C.; Nilsson, O.; Johansson, C.; Gendler, S.J.; Lindholm, L. Purification and characterization of a membrane-bound and a secreted mucin-type glycoprotein carrying the carcinoma-associated sialyl-Lea epitope on distinct core proteins. J. Biol. Chem., 1991, 266(32), 21537-21547.
50. Kelly, K.A.; Bardeesy, N.; Anbazhagan, R.; Gurumurthy, S.; Berger, J.; Alencar, H.; Depinho, R.A.; Mahmood, U.; Weissleder, R. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med., 2008, 5(4), e85.
51. Haug, U.; Wente, M.N.; Seiler, C.M.; Jesenofsky, R.; Brenner, H. Stool testing for the early detection of pancreatic cancer: Rationale and current evidence. Expert Rev. Mol. Diagn., 2008, 8(6), 753-759.
52. Xu, J.; Cao, Z.; Liu, W.; You, L.; Zhou, L.; Wang, C.; Lou, W.; Sun, B.; Miao, Y.; Liu, X.; Zhang, T.; Zhao, Y. Plasma miRNAs effectively distinguish patients with pancreatic cancer from controls: A multicenter study. Ann. Surg., 2016, 263(6), 1173-1179.
53. Abue, M.; Yokoyama, M.; Shibuya, R.; Tamai, K.; Yamaguchi, K.; Sato, I.; Tanaka, N.; Hamada, S.; Shimosegawa, T.; Sugamura, K.; Satoh, K. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int. J. Oncol., 2015, 46(2), 539-547.
54. Wang, C.; Sun, Y.; Wu, H.; Yu, S.; Zhang, L.; Meng, Y.; Liu, M.; Yang, H.; Liu, P.; Mao, X.; Lu, Z.; Chen, J. Elevated miR-483-3p expression is an early event and indicates poor prognosis in pancreatic ductal adenocarcinoma. Tumour Biol., 2015, 36(12), 9447-9456.
55. Brandi, J.; Dalla Pozza, E.; Dando, I.; Biondani, G.; Robotti, E.; Jenkins, R.; Elliott, V.; Park, K.; Marengo, E.; Costello, E.; Scarpa, A.; Palmieri, M.; Cecconi, D. Secretome protein signature of human pancreatic cancer stemlike cells. J. Proteomics, 2016, 136(136), 1-12.
56. Melo, S.A.; Luecke, L.B.; Kahlert, C.; Fernandez, A.F.; Gammon, S.T.; Kaye, J.; LeBleu, V.S.; Mittendorf, E.A.; Weitz, J.; Rahbari, N.; Reissfelder, C.; Pilarsky, C.; Fraga, M.F.; Piwnica-Worms, D.; Kalluri, R. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature, 2015, 523(7559), 177-182.
57. Bartsch, D.K.; Slater, E.P.; Carrato, A.; Ibrahim, I.S.; Guillen-Ponce, C.; Vasen, H.F.; Matthäi, E.; Earl, J.; Jendryschek, F.S.; Figiel, J.; Steinkamp, M.; Ramaswamy, A.; Vázquez-Sequeiros, E.; Muñoz-Beltran, M.; Montans, J.; Mocci, E.; Bonsing, B.A.; Wasser, M.; Klöppel, G.; Langer, P.; Fendrich, V.; Gress, T.M. Refinement of screening for familial pancreatic cancer. Gut, 2016, 65(8), 1314-1321.
58. Bartsch, D.K.; Dietzel, K.; Bargello, M.; Matthaei, E.; Kloeppel, G.; Esposito, I.; Heverhagen, J.T.; Gress, T.M.; Slater, E.P.; Langer, P. Multiple small “imaging” branchduct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia? Fam. Cancer, 2013, 12(1), 89-96.
59. Maire, F.; Couvelard, A.; Palazzo, L.; Aubert, A.; Vullierme, M.P.; Rebours, V.; Hammel, P.; Sauvanet, A.; Levy, P.; Ruszniewski, P. Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms: the interest of endoscopic ultrasonography. Pancreas, 2013, 42(8), 1262-1266.
60. Collins, M.A.; Neafsey, E.J.; Matsubara, K.; Cobuzzi, R.J., Jr; Rollema, H. Indole-N-methylated beta-carbolinium ions as potential brain-bioactivated neurotoxins. Brain Res., 1992, 570(1-2), 154-160.
61. Rahib, L.; Smith, B.D.; Aizenberg, R.; Rosenzweig, A.B.; Fleshman, J.M.; Matrisian, L.M. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res., 2014, 74(11), 2913-2921.
62. van Asperen, C.J.; Brohet, R.M.; Meijers-Heijboer, E.J.; Hoogerbrugge, N.; Verhoef, S.; Vasen, H.F.; Ausems, M.G.; Menko, F.H.; Gomez Garcia, E.B.; Klijn, J.G.; Hogervorst, F.B.; van Houwelingen, J.C.; van’t Veer, L.J.; Rookus, M.A.; van Leeuwen, F.E. Cancer risks in BRCA2 families: Estimates for sites other than breast and ovary. J. Med. Genet., 2005, 42(9), 711-719.
63. Thompson, D.; Easton, D.F. Cancer Incidence in BRCA1 mutation carriers. J. Natl. Cancer Inst., 2002, 94(18), 1358-1365.
64. Kastrinos, F.; Mukherjee, B.; Tayob, N.; Wang, F.; Sparr, J.; Raymond, V.M.; Bandipalliam, P.; Stoffel, E.M.; Gruber, S.B.; Syngal, S. Risk of pancreatic cancer in families with Lynch syndrome. JAMA, 2009, 302(16), 1790-1795.
65. Petersen, G.M.; Amundadottir, L.; Fuchs, C.S.; Kraft, P.; Stolzenberg-Solomon, R.Z.; Jacobs, K.B.; Arslan, A.A.; Bueno-de-Mesquita, H.B.; Gallinger, S.; Gross, M.; Helzlsouer, K.; Holly, E.A.; Jacobs, E.J.; Klein, A.P.; LaCroix, A.; Li, D.; Mandelson, M.T.; Olson, S.H.; Risch, H.A.; Zheng, W.; Albanes, D.; Bamlet, W.R.; Berg, C.D.; Boutron-Ruault, M.C.; Buring, J.E.; Bracci, P.M.; Canzian, F.; Clipp, S.; Cotterchio, M.; de Andrade, M.; Duell, E.J.; Gaziano, J.M.; Giovannucci, E.L.; Goggins, M.; Hallmans, G.; Hankinson, S.E.; Hassan, M.; Howard, B.; Hunter, D.J.; Hutchinson, A.; Jenab, M.; Kaaks, R.; Kooperberg, C.; Krogh, V.; Kurtz, R.C.; Lynch, S.M.; McWilliams, R.R.; Mendelsohn, J.B.; Michaud, D.S.; Parikh, H.; Patel, A.V.; Peeters, P.H.; Rajkovic, A.; Riboli, E.; Rodriguez, L.; Seminara, D.; Shu, X.O.; Thomas, G.; Tjønneland, A.; Tobias, G.S.; Trichopoulos, D.; Van Den Eeden, S.K.; Virtamo, J.; Wactawski-Wende, J.; Wang, Z.; Wolpin, B.M.; Yu, H.; Yu, K.; Zeleniuch-Jacquotte, A.; Fraumeni, J.F., Jr; Hoover, R.N.; Hartge, P.; Chanock, S.J. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet., 2010, 42(3), 224-228.
66. Becker, A.E.; Hernandez, Y.G.; Frucht, H.; Lucas, A.L. Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection. World J. Gastroenterol., 2014, 20(32), 11182-11198.
67. Lener, M.R.; Scott, R.J.; Kluzniak, W.; Baszuk, P.; Cybulski, C.; Wiechowska-Kozlowska, A.; Huzarski, T.; Byrski, T.; Kladny, J.; Pietrzak, S.; Soluch, A.; Jakubowska, A.; Lubinski, J. Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer? Int. J. Cancer, 2016, 139(3), 601-606.
68. Hu, C.; Hart, S.N.; Bamlet, W.R.; Moore, R.M.; Nandakumar, K.; Eckloff, B.W.; Lee, Y.K.; Petersen, G.M.; McWilliams, R.R.; Couch, F.J. Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Cancer Epidemiol. Biomarkers Prev., 2016, 25(1), 207-211.
69. Slater, E.P.; Langer, P.; Niemczyk, E.; Strauch, K.; Butler, J.; Habbe, N.; Neoptolemos, J.P.; Greenhalf, W.; Bartsch, D.K. PALB2 mutations in European familial pancreatic cancer families. Clin. Genet., 2010, 78(5), 490-494.
70. Canto, M.I.; Harinck, F.; Hruban, R.H.; Offerhaus, G.J.; Poley, J.W.; Kamel, I.; Nio, Y.; Schulick, R.S.; Bassi, C.; Kluijt, I.; Levy, M.J.; Chak, A.; Fockens, P.; Goggins, M.; Bruno, M. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut, 2013, 62(3), 339-347.