Pancreatic Cancer

  • Yingtai Chen
  • Chengfeng Wang
  • Yawei ZhangEmail author


Pancreatic cancer is a fatal malignancy associated with rapid progression. One year relative survival rates are less than 30%, and nearly all patients die from the disease within 7 years of surgery. In 2012, it was estimated that 338,000 men and women were diagnosed with pancreatic cancer and 331,000 died of the disease. Although there have been improvements in the diagnosis and prognosis of pancreatic cancer, these changes are minor. Although smoking is the only established nonheritable risk factor for pancreatic cancer, only approximately 30% of the cases can be attributed to smoking. Despite the inconclusive results, obesity, diabetes, alcohol consumption, and chronic pancreatitis have also been suggested as risk factors for pancreatic cancer. Given this poorly understood etiology, prevention of this deadly disease remains a challenge.


Pancreatic cancer Occupational risk factors Chemical production Metal manufacturing Solvents Molecular markers 


  1. 1.
    Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. JOP. 2008;9(2):99–132.PubMedGoogle Scholar
  2. 2.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013., accessed on day/month/year.Google Scholar
  3. 3.
    David M, Lepage C, Jouve JL, Jooste V, Chauvenet M, Faivre J, et al. Management and prognosis of pancreatic cancer over a 30-year period. Br J Cancer. 2009;101(2):215–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Parkin DM. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011;105(Suppl 2):S2–5.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bosetti C, Bertuccio P, Negri E, La Vecchia C, Zeegers MP, Boffetta P. Pancreatic cancer: overview of descriptive epidemiology. Mol Carcinog. 2012;51(1):3–13.PubMedCrossRefGoogle Scholar
  6. 6.
    Dunphy EP. Pancreatic cancer: a review and update. Clin J Oncol Nurs. 2008;12(5):735–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Ojajarvi IA, Partanen TJ, Ahlbom A, Boffetta P, Hakulinen T, Jourenkova N, et al. Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med. 2000;57(5):316–24.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Seilkop SK. Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med. 2001;58(1):63–4.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Chiazze L Jr, Ference LD. Mortality among PVC-fabricating employees. Environ Health Perspect. 1981;41:137–43.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Decoufle P. Further analysis of cancer mortality patterns among workers exposed to cutting oil mists. J Natl Cancer Inst. 1978;61(4):1025–30.PubMedGoogle Scholar
  11. 11.
    Hanis NM, Holmes TM, Shallenberger G, Jones KE. Epidemiologic study of refinery and chemical plant workers. J Occup Med. 1982;24(3):203–12.PubMedCrossRefGoogle Scholar
  12. 12.
    Li FP, Fraumeni JF Jr, Mantel N, Miller RW. Cancer mortality among chemists. J Natl Cancer Inst. 1969;43(5):1159–64.PubMedGoogle Scholar
  13. 13.
    Milham S Jr. Cancer mortality pattern associated with exposure to metals. Ann N Y Acad Sci. 1976;271:243–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Acheson ED, Gardner MJ, Winter PD, Bennett C. Cancer in a factory using amosite asbestos. Int J Epidemiol. 1984;13(1):3–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Bond GG, Reeve GR, Ott MG, Waxweiler RJ. Mortality among a sample of chemical company employees. Am J Ind Med. 1985;7(2):109–21.PubMedCrossRefGoogle Scholar
  16. 16.
    Decoufle P, Blattner WA, Blair A. Mortality among chemical workers exposed to benzene and other agents. Environ Res. 1983;30(1):16–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Elinder CG, Kjellstrom T, Hogstedt C, Andersson K, Spang G. Cancer mortality of cadmium workers. Br J Ind Med. 1985;42(10):651–5.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Howe GR, Fraser D, Lindsay J, Presnal B, Yu SZ. Cancer mortality (1965-77) in relation to diesel fume and coal exposure in a cohort of retired railway workers. J Natl Cancer Inst. 1983;70(6):1015–9.PubMedGoogle Scholar
  19. 19.
    Lynge E. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. Br J Cancer. 1985;52(2):259–70.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Milham S Jr. Mortality in workers exposed to electromagnetic fields. Environ Health Perspect. 1985;62:297–300.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Ott MG, Carlo GL, Steinberg S, Bond GG. Mortality among employees engaged in chemical manufacturing and related activities. Am J Epidemiol. 1985;122(2):311–22.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Rockette HE, Arena VC. Mortality studies of aluminum reduction plant workers: potroom and carbon department. J Occup Med. 1983;25(7):549–57.PubMedGoogle Scholar
  23. 23.
    Williams RR, Stegens NL, Goldsmith JR. Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview. J Natl Cancer Inst. 1977;59(4):1147–85.PubMedCrossRefGoogle Scholar
  24. 24.
    Acquavella J, Leet T, Johnson G. Occupational experience and mortality among a cohort of metal components manufacturing workers. Epidemiology. 1993;4(5):428–34.PubMedCrossRefGoogle Scholar
  25. 25.
    Benson LO, Teta MJ. Mortality due to pancreatic and lymphopoietic cancers in chlorohydrin production workers. Br J Ind Med. 1993;50(8):710–6.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Boffetta P, Stellman SD, Garfinkel L. Diesel exhaust exposure and mortality among males in the American Cancer Society prospective study. Am J Ind Med. 1988;14(4):403–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Brown DP. Mortality of workers exposed to polychlorinated biphenyls—an update. Arch Environ Health. 1987;42(6):333–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Coggon D, Pannett B, Winter PD, Acheson ED, Bonsall J. Mortality of workers exposed to 2 methyl-4 chlorophenoxyacetic acid. Scand J Work Environ Health. 1986;12(5):448–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Costantini AS, Paci E, Miligi L, Buiatti E, Martelli C, Lenzi S. Cancer mortality among workers in the Tuscan tanning industry. Br J Ind Med. 1989;46(6):384–8.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Enterline PE, Hartley J, Henderson V. Asbestos and cancer: a cohort followed up to death. Br J Ind Med. 1987;44(6):396–401.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Gardner MJ, Pannett B, Winter PD, Cruddas AM. A cohort study of workers exposed to formaldehyde in the British chemical industry: an update. Br J Ind Med. 1993;50(9):827–34.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Gustavsson P, Reuterwall C. Mortality and incidence of cancer among Swedish gas workers. Br J Ind Med. 1990;47(3):169–74.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Hansen ES. Mortality of auto mechanics. A ten-year follow-up. Scand J Work Environ Health. 1989;15(1):43–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Hearne FT, Pifer JW, Grose F. Absence of adverse mortality effects in workers exposed to methylene chloride: an update. J Occup Med. 1990;32(3):234–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Lanes SF, Rothman KJ, Dreyer NA, Soden KJ. Mortality update of cellulose fiber production workers. Scand J Work Environ Health. 1993;19(6):426–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Langard S, Andersen A, Ravnestad J. Incidence of cancer among ferrochromium and ferrosilicon workers: an extended observation period. Br J Ind Med. 1990;47(1):14–9.PubMedPubMedCentralGoogle Scholar
  37. 37.
    McDonald JC, Liddell FD, Dufresne A, McDonald AD. The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88. Br J Ind Med. 1993;50(12):1073–81.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Silverstein M, Park R, Marmor M, Maizlish N, Mirer F. Mortality among bearing plant workers exposed to metalworking fluids and abrasives. J Occup Med. 1988;30(9):706–14.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Smulevich VB, Fedotova IV, Filatova VS. Increasing evidence of the rise of cancer in workers exposed to vinylchloride. Br J Ind Med. 1988;45(2):93–7.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Vena JE, Sultz HA, Fiedler RC, Barnes RE. Mortality of workers in an automobile engine and parts manufacturing complex. Br J Ind Med. 1985;42(2):85–93.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Wen CP, Tsai SP, Weiss NS, Gibson RL, Wong O, McClellan WA. Long-term mortality study of oil refinery workers. IV. Exposure to the lubricating-dewaxing process. J Natl Cancer Inst. 1985;74(1):11–8.PubMedGoogle Scholar
  42. 42.
    Wong O. An industry wide mortality study of chemical workers occupationally exposed to benzene. I. General results. Br J Ind Med. 1987;44(6):365–81.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Zoloth SR, Michaels DM, Villalbi JR, Lacher M. Patterns of mortality among commercial pressmen. J Natl Cancer Inst. 1986;76(6):1047–51.PubMedGoogle Scholar
  44. 44.
    Anttila A, Pukkala E, Sallmen M, Hernberg S, Hemminki K. Cancer incidence among Finnish workers exposed to halogenated hydrocarbons. J Occup Environ Med. 1995;37(7):797–806.PubMedCrossRefGoogle Scholar
  45. 45.
    Asp S, Riihimaki V, Hernberg S, Pukkala E. Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up. Am J Ind Med. 1994;26(2):243–53.PubMedCrossRefGoogle Scholar
  46. 46.
    Axelson O, Selden A, Andersson K, Hogstedt C. Updated and expanded Swedish cohort study on trichloroethylene and cancer risk. J Occup Med. 1994;36(5):556–62.PubMedGoogle Scholar
  47. 47.
    Baris D, Armstrong BG, Deadman J, Theriault G. A mortality study of electrical utility workers in Quebec. Occup Environ Med. 1996;53(1):25–31.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Boffetta P, Saracci R, Andersen A, Bertazzi PA, Chang-Claude J, Cherrie J, et al. Cancer mortality among man-made vitreous fiber production workers. Epidemiology. 1997;8(3):259–68.PubMedCrossRefGoogle Scholar
  49. 49.
    Brown DP, Dement JM, Okun A. Mortality patterns among female and male chrysotile asbestos textile workers. J Occup Med. 1994;36(8):882–8.PubMedGoogle Scholar
  50. 50.
    Alguacil J, Pollan M, Gustavsson P. Occupations with increased risk of pancreatic cancer in the Swedish population. Occup Environ Med. 2003;60(8):570–6.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Anttila A, Pukkala E, Riala R, Sallmen M, Hemminki K. Cancer incidence among Finnish workers exposed to aromatic hydrocarbons. Int Arch Occup Environ Health. 1998;71(3):187–93.PubMedCrossRefGoogle Scholar
  52. 52.
    Cocco P, Blair A, Congia P, Saba G, Ecca AR, Palmas C. Long-term health effects of the occupational exposure to DDT. A preliminary report. Ann N Y Acad Sci. 1997;837:246–56.PubMedCrossRefGoogle Scholar
  53. 53.
    Cocco P, Hua F, Boffetta P, Carta P, Flore C, Flore V, et al. Mortality of Italian lead smelter workers. Scand J Work Environ Health. 1997;23(1):15–23.PubMedCrossRefGoogle Scholar
  54. 54.
    Enterline PE, Day R, Marsh GM. Cancers related to exposure to arsenic at a copper smelter. Occup Environ Med. 1995;52(1):28–32.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Gibbs GW, Amsel J, Soden K. A cohort mortality study of cellulose triacetate-fiber workers exposed to methylene chloride. J Occup Environ Med. 1996;38(7):693–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Hansen J, Olsen JH. Formaldehyde and cancer morbidity among male employees in Denmark. Cancer Causes Control. 1995;6(4):354–60.PubMedCrossRefGoogle Scholar
  57. 57.
    Wong O, Trent LS, Whorton MD. An updated cohort mortality study of workers exposed to styrene in the reinforced plastics and composites industry. Occup Environ Med. 1994;51(6):386–96.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Yassi A, Tate R, Fish D. Cancer mortality in workers employed at a transformer manufacturing plant. Am J Ind Med. 1994;25(3):425–37.PubMedCrossRefGoogle Scholar
  59. 59.
    Hooiveld M, Heederik DJ, Kogevinas M, Boffetta P, Needham LL, Patterson DG Jr, et al. Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides, chlorophenols, and contaminants. Am J Epidemiol. 1998;147(9):891–901.PubMedCrossRefGoogle Scholar
  60. 60.
    Jarup L, Bellander T, Hogstedt C, Spang G. Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel. Occup Environ Med. 1998;55(11):755–9.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, Bueno-de-Mesquita HB, et al. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. Am J Epidemiol. 1997;145(12):1061–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Rafnsson V. Incidence of cancer among bookbinders, printers, photoengravers, and typesetters. Occup Environ Med. 2001;58(8):523–7.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Sathiakumar N, Delzell E, Hovinga M, Macaluso M, Julian JA, Larson R, et al. Mortality from cancer and other causes of death among synthetic rubber workers. Occup Environ Med. 1998;55(4):230–5.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Wiebelt H, Becker N. Mortality in a cohort of toluene exposed employees (rotogravure printing plant workers). J Occup Environ Med. 1999;41(12):1134–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Alguacil J, Porta M, Benavides FG, Malats N, Kogevinas M, Fernandez E, et al. Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group. Int J Epidemiol. 2000;29(6):1004–13.PubMedCrossRefGoogle Scholar
  66. 66.
    Alguacil J, Porta M, Malats N, Kauppinen T, Kogevinas M, Benavides FG, et al. Occupational exposure to organic solvents and K-ras mutations in exocrine pancreatic cancer. Carcinogenesis. 2002;23(1):101–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Bardin JA, Eisen EA, Tolbert PE, Hallock MF, Hammond SK, Woskie SR, et al. Mortality studies of machining fluid exposure in the automobile industry. V: a case-control study of pancreatic cancer. Am J Ind Med. 1997;32(3):240–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Falk RT, Pickle LW, Fontham ET, Correa P, Morse A, Chen V, et al. Occupation and pancreatic cancer risk in Louisiana. Am J Ind Med. 1990;18(5):565–76.PubMedCrossRefGoogle Scholar
  69. 69.
    Garabrant DH, Held J, Langholz B, Peters JM, Mack TM. DDT and related compounds and risk of pancreatic cancer. J Natl Cancer Inst. 1992;84(10):764–71.PubMedCrossRefGoogle Scholar
  70. 70.
    Ji BT, Silverman DT, Dosemeci M, Dai Q, Gao YT, Blair A. Occupation and pancreatic cancer risk in Shanghai, China. Am J Ind Med. 1999;35(1):76–81.PubMedCrossRefGoogle Scholar
  71. 71.
    Lin RS, Kessler II. A multifactorial model for pancreatic cancer in man. Epidemiologic evidence. JAMA. 1981;245(2):147–52.PubMedCrossRefGoogle Scholar
  72. 72.
    Mack TM, Peters JM, Yu MC, Hanisch R, Wright WE, Henderson BE. Pancreas cancer is unrelated to the workplace in Los Angeles. Am J Ind Med. 1985;7(3):253–66.PubMedCrossRefGoogle Scholar
  73. 73.
    Magnani C, Coggon D, Osmond C, Acheson ED. Occupation and five cancers: a case-control study using death certificates. Br J Ind Med. 1987;44(11):769–76.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Mallin K, Rubin M, Joo E. Occupational cancer mortality in Illinois white and black males, 1979-1984, for seven cancer sites. Am J Ind Med. 1989;15(6):699–717.PubMedCrossRefGoogle Scholar
  75. 75.
    Pickle LW, Gottlieb MS. Pancreatic cancer mortality in Louisiana. Am J Public Health. 1980;70(3):256–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Pietri F, Clavel F, Auquier A, Flamant R. Occupational risk factors for cancer of the pancreas: a case-control study. Br J Ind Med. 1990;47(6):425–8.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Kauppinen T, Partanen T, Degerth R, Ojajarvi A. Pancreatic cancer and occupational exposures. Epidemiology. 1995;6(5):498–502.PubMedCrossRefGoogle Scholar
  78. 78.
    Kernan GJ, Ji BT, Dosemeci M, Silverman DT, Balbus J, Zahm SH. Occupational risk factors for pancreatic cancer: a case-control study based on death certificates from 24 U.S. states. Am J Ind Med. 1999;36(2):260–70.PubMedCrossRefGoogle Scholar
  79. 79.
    Mikoczy Z, Schutz A, Stromberg U, Hagmar L. Cancer incidence and specific occupational exposures in the Swedish leather tanning industry: a cohort based case-control study. Occup Environ Med. 1996;53(7):463–7.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Partanen T, Kauppinen T, Degerth R, Moneta G, Mearelli I, Ojajarvi A, et al. Pancreatic cancer in industrial branches and occupations in Finland. Am J Ind Med. 1994;25(6):851–66.PubMedCrossRefGoogle Scholar
  81. 81.
    Santibanez M, Vioque J, Alguacil J, de la Hera MG, Moreno-Osset E, Carrato A, et al. Occupational exposures and risk of pancreatic cancer. Eur J Epidemiol. 2010;25(10):721–30.PubMedCrossRefGoogle Scholar
  82. 82.
    Selenskas S, Teta MJ, Vitale JN. Pancreatic cancer among workers processing synthetic resins. Am J Ind Med. 1995;28(3):385–98.PubMedCrossRefGoogle Scholar
  83. 83.
    Zhang Y, Cantor KP, Lynch CF, Zhu Y, Zheng T. Occupation and risk of pancreatic cancer: a population-based case-control study in Iowa. J Occup Environ Med. 2005;47(4):392–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Milham S. Occupational mortality in Washington state, 1950–1989. Cincinnati: DHHS (NIOSH); 1997.Google Scholar
  85. 85.
    Ojajarvi A, Partanen T, Ahlbom A, Hakulinen T, Kauppinen T, Weiderpass E, et al. Estimating the relative risk of pancreatic cancer associated with exposure agents in job title data in a hierarchical Bayesian meta-analysis. Scand J Work Environ Health. 2007;33(5):325–35.PubMedCrossRefGoogle Scholar
  86. 86.
    Maruchi N, Brian D, Ludwig J, Elveback LR, Kurland LT. Cancer of the pancreas in Olmsted County, Minnesota, 1935-1974. Mayo Clin Proc. 1979;54(4):245–9.PubMedGoogle Scholar
  87. 87.
    Boffetta P, Jourenkova N, Gustavsson P. Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control. 1997;8(3):444–72.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Andreotti G, Silverman DT. Occupational risk factors and pancreatic cancer: a review of recent findings. Mol Carcinog. 2012;51(1):98–108.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lloyd JW, Decoufle P, Salvin LG. Unusual mortality experience of printing pressmen. J Occup Med. 1977;19(8):543–50.PubMedGoogle Scholar
  90. 90.
    Wingren G, Persson B, Thoren K, Axelson O. Mortality pattern among pulp and paper mill workers in Sweden: a case-referent study. Am J Ind Med. 1991;20(6):769–74.PubMedCrossRefGoogle Scholar
  91. 91.
    Mastrangelo G, Fadda E, Marzia V. Polycyclic aromatic hydrocarbons and cancer in man. Environ Health Perspect. 1996;104(11):1166–70.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Calvert GM, Ward E, Schnorr TM, Fine LJ. Cancer risks among workers exposed to metalworking fluids: a systematic review. Am J Ind Med. 1998;33(3):282–92.PubMedCrossRefGoogle Scholar
  93. 93.
    Milham S. Occupational mortality in Washington state, 1950–1979. Washington, DC: US NIOSH; 1983.Google Scholar
  94. 94.
    Li W, Ray RM, Gao DL, Fitzgibbons ED, Seixas NS, Camp JE, et al. Occupational risk factors for pancreatic cancer among female textile workers in Shanghai, China. Occup Environ Med. 2006;63(12):788–93.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Cantor KP, Silberman W. Mortality among aerial pesticide applicators and flight instructors: follow-up from 1965-1988. Am J Ind Med. 1999;36(2):239–47.PubMedCrossRefGoogle Scholar
  96. 96.
    Porta M, Malats N, Jariod M, Grimalt JO, Rifa J, Carrato A, et al. Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group. Lancet. 1999;354(9196):2125–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Hanley AJ, Johnson KC, Villeneuve PJ, Mao Y, Canadian Cancer Registries Epidemiology Research Group. Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer. 2001;94(1):140–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Stolzenberg-Solomon RZ, Pietinen P, Taylor PR, Virtamo J, Albanes D. A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control. 2002;13(5):417–26.PubMedCrossRefGoogle Scholar
  99. 99.
    O’Rorke MA, Cantwell MM, Cardwell CR, Mulholland HG, Murray LJ. Can physical activity modulate pancreatic cancer risk? A systematic review and meta-analysis. Int J Cancer. 2010;126(12):2957–68.PubMedGoogle Scholar
  100. 100.
    Iodice S, Gandini S, Maisonneuve P, Lowenfels AB. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbeck’s Arch Surg. 2008;393(4):535–45.CrossRefGoogle Scholar
  101. 101.
    Lynch SM, Vrieling A, Lubin JH, Kraft P, Mendelsohn JB, Hartge P, et al. Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol. 2009;170(4):403–13.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Brownson RC, Figgs LW, Caisley LE. Epidemiology of environmental tobacco smoke exposure. Oncogene. 2002;21(48):7341–8.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Gallicchio L, Kouzis A, Genkinger JM, Burke AE, Hoffman SC, Diener-West M, et al. Active cigarette smoking, household passive smoke exposure, and the risk of developing pancreatic cancer. Prev Med. 2006;42(3):200–5.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Tranah GJ, Holly EA, Wang F, Bracci PM. Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area. BMC Cancer. 2011;11:138.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Villeneuve PJ, Johnson KC, Mao Y, Hanley AJ, Canadian Cancer registries research Group. Environmental tobacco smoke and the risk of pancreatic cancer: findings from a Canadian population-based case-control study. Can J Public Health. 2004;95(1):32–7.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Vrieling A, Bueno-de-Mesquita HB, Boshuizen HC, Michaud DS, Severinsen MT, Overvad K, et al. Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2010;126(10):2394–403.PubMedPubMedCentralGoogle Scholar
  107. 107.
    International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans, vol. 96. Alcohol consumption and ethyl carbamate. Lyon: International Agency for Research on Cancer; 2010.Google Scholar
  108. 108.
    Cuzick J, Babiker AG. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. Int J Cancer. 1989;43(3):415–21.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Falk RT, Pickle LW, Fontham ET, Correa P, Fraumeni JF Jr. Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. Am J Epidemiol. 1988;128(2):324–36.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Harnack LJ, Anderson KE, Zheng W, Folsom AR, Sellers TA, Kushi LH. Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women’s Health Study. Cancer Epidemiol Biomark Prev. 1997;6(12):1081–6.Google Scholar
  111. 111.
    Hassan MM, Bondy ML, Wolff RA, Abbruzzese JL, Vauthey JN, Pisters PW, et al. Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol. 2007;102(12):2696–707.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Heinen MM, Verhage BA, Ambergen TA, Goldbohm RA, van den Brandt PA. Alcohol consumption and risk of pancreatic cancer in the Netherlands cohort study. Am J Epidemiol. 2009;169(10):1233–42.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Heuch I, Kvale G, Jacobsen BK, Bjelke E. Use of alcohol, tobacco and coffee, and risk of pancreatic cancer. Br J Cancer. 1983;48(5):637–43.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Jiao L, Silverman DT, Schairer C, Thiebaut AC, Hollenbeck AR, Leitzmann MF, et al. Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study. Am J Epidemiol. 2009;169(9):1043–51.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM. A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet. Am J Public Health. 1989;79(8):1016–9.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Silverman DT, Brown LM, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB, et al. Alcohol and pancreatic cancer in blacks and whites in the United States. Cancer Res. 1995;55(21):4899–905.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Suzuki T, Matsuo K, Sawaki A, Mizuno N, Hiraki A, Kawase T, et al. Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk. Cancer Epidemiol Biomark Prev. 2008;17(10):2742–7.CrossRefGoogle Scholar
  118. 118.
    Talamini R, Polesel J, Gallus S, Dal Maso L, Zucchetto A, Negri E, et al. Tobacco smoking, alcohol consumption and pancreatic cancer risk: a case-control study in Italy. Eur J Cancer. 2010;46(2):370–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Zheng W, McLaughlin JK, Gridley G, Bjelke E, Schuman LM, Silverman DT, et al. A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States). Cancer Causes Control. 1993;4(5):477–82.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Lucenteforte E, La Vecchia C, Silverman D, Petersen GM, Bracci PM, Ji BT, et al. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012;23(2):374–82.PubMedCrossRefGoogle Scholar
  121. 121.
    MacMahon B, Yen S, Trichopoulos D, Warren K, Nardi G. Coffee and cancer of the pancreas. N Engl J Med. 1981;304(11):630–3.PubMedCrossRefGoogle Scholar
  122. 122.
    Dong J, Zou J, Yu XF. Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies. World J Gastroenterol. 2011;17(9):1204–10.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Turati F, Galeone C, Edefonti V, Ferraroni M, Lagiou P, La Vecchia C, et al. A meta-analysis of coffee consumption and pancreatic cancer. Ann Oncol. 2012;23(2):311–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Ran HQ, Wang JZ, Sun CQ. Coffee consumption and pancreatic cancer risk: an update meta-analysis of cohort studies. Pak J Med Sci. 2016;32(1):253–9.PubMedPubMedCentralGoogle Scholar
  125. 125.
    World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington, DC: AICR; 2007. p. 211–42.Google Scholar
  126. 126.
    Genkinger JM, Spiegelman D, Anderson KE, Bernstein L, van den Brandt PA, Calle EE, et al. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 2011;129(7):1708–17.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Aune D, Greenwood DC, Chan DS, Vieira R, Vieira AR, Navarro Rosenblatt DA, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. 2012;23(4):843–52.PubMedCrossRefGoogle Scholar
  128. 128.
    Chan JM, Wang F, Holly EA. Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area. Cancer Epidemiol Biomark Prev. 2005;14(9):2093–7.CrossRefGoogle Scholar
  129. 129.
    Mills PK, Beeson WL, Abbey DE, Fraser GE, Phillips RL. Dietary habits and past medical history as related to fatal pancreas cancer risk among adventists. Cancer. 1988;61(12):2578–85.PubMedCrossRefGoogle Scholar
  130. 130.
    Nkondjock A, Krewski D, Johnson KC, Ghadirian P, Canadian Cancer Registries Epidemiology Research Group. Dietary patterns and risk of pancreatic cancer. Int J Cancer. 2005;114(5):817–23.PubMedCrossRefGoogle Scholar
  131. 131.
    Shibata A, Mack TM, Paganini-Hill A, Ross RK, Henderson BE. A prospective study of pancreatic cancer in the elderly. Int J Cancer. 1994;58(1):46–9.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Silverman DT, Swanson CA, Gridley G, Wacholder S, Greenberg RS, Brown LM, et al. Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1998;90(22):1710–9.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Gong Z, Holly EA, Wang F, Chan JM, Bracci PM. Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Int J Cancer. 2010;127(8):1893–904.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Howe GR, Ghadirian P, Bueno de Mesquita HB, Zatonski WA, Baghurst PA, Miller AB, et al. A collaborative case-control study of nutrient intake and pancreatic cancer within the search programme. Int J Cancer. 1992;51(3):365–72.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Nkondjock A, Ghadirian P, Johnson KC, Krewski D, Canadian Cancer Registries Epidemiology Research Group. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr. 2005;135(3):592–7.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM. Nutrients and pancreatic cancer: a population-based case-control study. Cancer Causes Control. 1991;2(5):291–7.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Stolzenberg-Solomon RZ, Albanes D, Nieto FJ, Hartman TJ, Tangrea JA, Rautalahti M, et al. Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst. 1999;91(6):535–41.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Zatonski W, Przewozniak K, Howe GR, Maisonneuve P, Walker AM, Boyle P. Nutritional factors and pancreatic cancer: a case-control study from south-west Poland. Int J Cancer. 1991;48(3):390–4.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Chan JM, Wang F, Holly EA. Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California. Cancer Causes Control. 2007;18(10):1153–67.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Larsson SC, Hakanson N, Permert J, Wolk A. Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study. Int J Cancer. 2006;118(11):2866–70.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Nothlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst. 2005;97(19):1458–65.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Coughlin SS, Calle EE, Patel AV, Thun MJ. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000;11(10):915–23.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol. 2003;157(12):1115–25.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Larsson SC, Wolk A. Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. Br J Cancer. 2012;106(3):603–7.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Rohrmann S, Linseisen J, Nothlings U, Overvad K, Egeberg R, Tjonneland A, et al. Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2013;132(3):617–24.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Arem H, Mayne ST, Sampson J, Risch H, Stolzenberg-Solomon RZ. Dietary fat intake and risk of pancreatic cancer in the prostate, lung, colorectal and ovarian cancer screening trial. Ann Epidemiol. 2013;23(9):571–5.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Aschebrook-Kilfoy B, Cross AJ, Stolzenberg-Solomon RZ, Schatzkin A, Hollenbeck AR, Sinha R, et al. Pancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study. Am J Epidemiol. 2011;174(3):305–15.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr. 2016;103(1):218–30.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Bao Y, Hu FB, Giovannucci EL, Wolpin BM, Stampfer MJ, Willett WC, et al. Nut consumption and risk of pancreatic cancer in women. Br J Cancer. 2013;109(11):2911–6.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Wu L, Wang Z, Zhu J, Murad AL, Prokop LJ, Murad MH. Nut consumption and risk of cancer and type 2 diabetes: a systematic review and meta-analysis. Nutr Rev. 2015;73(7):409–25.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Wu QJ, Wu L, Zheng LQ, Xu X, Ji C, Gong TT. Consumption of fruit and vegetables reduces risk of pancreatic cancer: evidence from epidemiological studies. Eur J Cancer Prev. 2016;25(3):196–205.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Maisonneuve P, Lowenfels AB. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol. 2015;44(1):186–98.PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer. 2011;47(13):1928–37.PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Batabyal P, Vander Hoorn S, Christophi C, Nikfarjam M. Association of diabetes mellitus and pancreatic adenocarcinoma: a meta-analysis of 88 studies. Ann Surg Oncol. 2014;21(7):2453–62.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Haugvik SP, Hedenstrom P, Korsaeth E, Valente R, Hayes A, Siuka D, et al. Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis. Neuroendocrinology. 2015;101(2):133–42.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Stevens RJ, Roddam AW, Beral V. Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer. 2007;96(3):507–9.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993;328(20):1433–7.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Kudo Y, Kamisawa T, Anjiki H, Takuma K, Egawa N. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis. Hepato-Gastroenterology. 2011;58(106):609–11.PubMedPubMedCentralGoogle Scholar
  159. 159.
    Duell EJ, Lucenteforte E, Olson SH, Bracci PM, Li D, Risch HA, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the international pancreatic Cancer case-control consortium (PanC4). Ann Oncol. 2012;23(11):2964–70.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Lowenfels AB, Maisonneuve P, Whitcomb DC. Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group. Med Clin North Am. 2000;84(3):565–73.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Chen XZ, Schottker B, Castro FA, Chen H, Zhang Y, Holleczek B, et al. Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: a ten-year follow-up of the ESTHER cohort study. Oncotarget. 2016;7(13):17182–93.PubMedPubMedCentralGoogle Scholar
  162. 162.
    Freelove R, Walling AD. Pancreatic cancer: diagnosis and management. Am Fam Physician. 2006;73(3):485–92.PubMedGoogle Scholar
  163. 163.
    Lauwers GY, Mino-Kenudson M, Rubin R. In: Rubin R, Strayer D, editors. Rubin’s pathology: clinicopathologic foundations of medicine. Wolters Kluwer Lippincott Williams & Wilkins: Baltimore; 2008.Google Scholar
  164. 164.
    Malesci A, Montorsi M, Mariani A, Santambrogio R, Bonato C, Bissi O, et al. Clinical utility of the serum CA 19-9 test for diagnosing pancreatic carcinoma in symptomatic patients: a prospective study. Pancreas. 1992;7(4):497–502.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL. Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol. 1997;4(7):551–6.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, et al. Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res. 2004;10(7):2386–92.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    Koopmann J, Rosenzweig CN, Zhang Z, Canto MI, Brown DA, Hunter M, et al. Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9. Clin Cancer Res. 2006;12(2):442–6.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Koopmann J, Fedarko NS, Jain A, Maitra A, Iacobuzio-Donahue C, Rahman A, et al. Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol Biomark Prev. 2004;13(3):487–91.Google Scholar
  169. 169.
    Zhou W, Sokoll LJ, Bruzek DJ, Zhang L, Velculescu VE, Goldin SB, et al. Identifying markers for pancreatic cancer by gene expression analysis. Cancer Epidemiol Biomark Prev. 1998;7(2):109–12.Google Scholar
  170. 170.
    Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz RE, et al. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res. 2001;7(12):3862–8.PubMedPubMedCentralGoogle Scholar
  171. 171.
    Chen R, Pan S, Cooke K, Moyes KW, Bronner MP, Goodlett DR, et al. Comparison of pancreas juice proteins from cancer versus pancreatitis using quantitative proteomic analysis. Pancreas. 2007;34(1):70–9.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Gronborg M, Bunkenborg J, Kristiansen TZ, Jensen ON, Yeo CJ, Hruban RH, et al. Comprehensive proteomic analysis of human pancreatic juice. J Proteome Res. 2004;3(5):1042–55.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Rosty C, Goggins M. Early detection of pancreatic carcinoma. Hematol Oncol Clin North Am. 2002;16(1):37–52.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6(8):2969–72.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Mazaki T, Masuda H, Takayama T. Polymorphisms and pancreatic cancer risk: a meta-analysis. Eur J Cancer Prev. 2011;20(3):169–83.PubMedCrossRefGoogle Scholar
  176. 176.
    Wilentz RE, Iacobuzio-Donahue CA, Argani P, McCarthy DM, Parsons JL, Yeo CJ, et al. Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 2000;60(7):2002–6.PubMedGoogle Scholar
  177. 177.
    Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549–54.PubMedCrossRefGoogle Scholar
  178. 178.
    Aspinall RJ, Lemoine NR. Gene therapy for pancreatic and biliary malignancies. Ann Oncol. 1999;10(Suppl 4):188–92.PubMedCrossRefGoogle Scholar
  179. 179.
    Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997;57(15):3126–30.PubMedGoogle Scholar
  180. 180.
    Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003;186(3):279–86.PubMedCrossRefGoogle Scholar
  181. 181.
    Sohn TA, Yeo CJ. The molecular genetics of pancreatic ductal carcinoma: a review. Surg Oncol. 2000;9(3):95–101.PubMedCrossRefGoogle Scholar
  182. 182.
    Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006;20(2):197–209.PubMedCrossRefGoogle Scholar
  183. 183.
    Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363(9414):1049–57.PubMedCrossRefGoogle Scholar
  184. 184.
    Bartsch H, Malaveille C, Lowenfels AB, Maisonneuve P, Hautefeuille A, Boyle P. Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk. The International Pancreatic Disease Study Group. Eur J Cancer Prev. 1998;7(3):215–23.PubMedCrossRefGoogle Scholar
  185. 185.
    Duell EJ, Holly EA, Bracci PM, Liu M, Wiencke JK, Kelsey KT. A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J Natl Cancer Inst. 2002;94(4):297–306.PubMedCrossRefGoogle Scholar
  186. 186.
    Jiao L, Hassan MM, Bondy ML, Abbruzzese JL, Evans DB, Li D. The XPD Asp312Asn and Lys751Gln polymorphisms, corresponding haplotype, and pancreatic cancer risk. Cancer Lett. 2007;245(1–2):61–8.PubMedCrossRefGoogle Scholar
  187. 187.
    Lee HC, Yoon YB, Kim CY. Association between genetic polymorphisms of the cytochromes P-450 (1A1, 2D6, and 2E1) and the susceptibility to pancreatic cancer. Korean J Intern Med. 1997;12(2):128–36.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Li D, Jiao L, Li Y, Doll MA, Hein DW, Bondy ML, et al. Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer. Carcinogenesis. 2006;27(1):103–11.PubMedCrossRefGoogle Scholar
  189. 189.
    Liu G, Ghadirian P, Vesprini D, Hamel N, Paradis AJ, Lal G, et al. Polymorphisms in GSTM1, GSTT1 and CYP1A1 and risk of pancreatic adenocarcinoma. Br J Cancer. 2000;82(10):1646–9.PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Ockenga J, Vogel A, Teich N, Keim V, Manns MP, Strassburg CP. UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer. Gastroenterology. 2003;124(7):1802–8.PubMedCrossRefGoogle Scholar
  191. 191.
    Piepoli A, Gentile A, Valvano MR, Barana D, Oliani C, Cotugno R, et al. Lack of association between UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms and pancreatic cancer in Italian patients. World J Gastroenterol. 2006;12(39):6343–8.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Verlaan M, Drenth JP, Truninger K, Koudova M, Schulz HU, Bargetzi M, et al. Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases. J Med Genet. 2005;42(10):e62.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Vrana D, Pikhart H, Mohelnikova-Duchonova B, Holcatova I, Strnad R, Slamova A, et al. The association between glutathione S-transferase gene polymorphisms and pancreatic cancer in a central European Slavonic population. Mutat Res. 2009;680(1–2):78–81.PubMedCrossRefGoogle Scholar
  194. 194.
    Duell EJ, Holly EA, Bracci PM, Wiencke JK, Kelsey KT. A population-based study of the Arg399Gln polymorphism in X-ray repair cross- complementing group 1 (XRCC1) and risk of pancreatic adenocarcinoma. Cancer Res. 2002;62(16):4630–6.PubMedGoogle Scholar
  195. 195.
    Jiao L, Bondy ML, Hassan MM, Wolff RA, Evans DB, Abbruzzese JL, et al. Selected polymorphisms of DNA repair genes and risk of pancreatic cancer. Cancer Detect Prev. 2006;30(3):284–91.PubMedCrossRefGoogle Scholar
  196. 196.
    Jiao L, Hassan MM, Bondy ML, Wolff RA, Evans DB, Abbruzzese JL, et al. XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. Am J Gastroenterol. 2008;103(2):360–7.PubMedCrossRefGoogle Scholar
  197. 197.
    Li D, Suzuki H, Liu B, Morris J, Liu J, Okazaki T, et al. DNA repair gene polymorphisms and risk of pancreatic cancer. Clin Cancer Res. 2009;15(2):740–6.PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    McWilliams RR, Bamlet WR, Cunningham JM, Goode EL, de Andrade M, Boardman LA, et al. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res. 2008;68(12):4928–35.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Wang L, Lin DX, Lu XH, Miao XP, Li H. Polymorphisms of the DNA repair genes XRCC1 and XPC: relationship to pancreatic cancer risk. Wei Sheng Yan Jiu. 2006;35(5):534–6.PubMedGoogle Scholar
  200. 200.
    Duell EJ, Casella DP, Burk RD, Kelsey KT, Holly EA. Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiol Biomark Prev. 2006;15(4):726–31.CrossRefGoogle Scholar
  201. 201.
    Reid-Lombardo KM, Fridley BL, Bamlet WR, Cunningham JM, Sarr MG, Petersen GM. Inflammation-related gene variants as risk factors for pancreatic cancer. Cancer Epidemiol Biomark Prev. 2011;20(6):1251–4.CrossRefGoogle Scholar
  202. 202.
    Kanda J, Matsuo K, Suzuki T, Kawase T, Hiraki A, Watanabe M, et al. Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese. Cancer Sci. 2009;100(2):296–302.PubMedCrossRefGoogle Scholar
  203. 203.
    Miyasaka K, Kawanami T, Shimokata H, Ohta S, Funakoshi A. Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among smokers in a Japanese male population. Pancreas. 2005;30(2):95–8.PubMedCrossRefGoogle Scholar
  204. 204.
    Li D, Ahmed M, Li Y, Jiao L, Chou TH, Wolff RA, et al. 5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol Biomark Prev. 2005;14(6):1470–6.CrossRefGoogle Scholar
  205. 205.
    Matsubayashi H, Skinner HG, Iacobuzio-Donahue C, Abe T, Sato N, Riall TS, et al. Pancreaticobiliary cancers with deficient methylenetetrahydrofolate reductase genotypes. Clin Gastroenterol Hepatol. 2005;3(8):752–60.PubMedCrossRefGoogle Scholar
  206. 206.
    Wang L, Miao X, Tan W, Lu X, Zhao P, Zhao X, et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer. Clin Gastroenterol Hepatol. 2005;3(8):743–51.PubMedCrossRefGoogle Scholar
  207. 207.
    Lempinen M, Paju A, Kemppainen E, Smura T, Kylanpaa ML, Nevanlinna H, et al. Mutations N34S and P55S of the SPINK1 gene in patients with chronic pancreatitis or pancreatic cancer and in healthy subjects: a report from Finland. Scand J Gastroenterol. 2005;40(2):225–30.PubMedCrossRefGoogle Scholar
  208. 208.
    Matsubayashi H, Fukushima N, Sato N, Brune K, Canto M, Yeo CJ, et al. Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial pancreatic cancer. Cancer Biol Ther. 2003;2(6):652–5.PubMedCrossRefGoogle Scholar
  209. 209.
    Teich N, Schulz HU, Witt H, Bohmig M, Keim V. N34S, a pancreatitis associated SPINK1 mutation, is not associated with sporadic pancreatic cancer. Pancreatology. 2003;3(1):67–8.PubMedCrossRefGoogle Scholar
  210. 210.
    Dong X, Li Y, Chang P, Tang H, Hess KR, Abbruzzese JL, et al. Glucose metabolism gene variants modulate the risk of pancreatic cancer. Cancer Prev Res (Phila). 2011;4(5):758–66.CrossRefGoogle Scholar
  211. 211.
    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(9):986–90.PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    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(3):224–8.PubMedPubMedCentralCrossRefGoogle Scholar
  213. 213.
    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(9):994–1000.PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    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(8):911–6.PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet. 2011;44(1):62–6.PubMedCrossRefGoogle Scholar
  216. 216.
    Low SK, Kuchiba A, Zembutsu H, Saito A, Takahashi A, Kubo M, et al. Genome-wide association study of pancreatic cancer in Japanese population. PLoS One. 2010;5(7):e11824.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Pancreatic and Gastric SurgeryNational Cancer Center, Cancer Hospital, Chinese Academy of Medical SciencesBeijingChina
  2. 2.Section of Surgical Outcomes and Epidemiology, Department of SurgeryYale School of MedicineNew HavenUSA
  3. 3.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA

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