Molecular Epidemiology

  • Donghui Li
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)


The severity of the pancreatic cancer problem and the scarcity of information on its etiology call for more research effort. Epidemiological studies have found that the incidence and mortality of pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in males than females and higher in blacks than whites. Both genetic and environmental factors may play significant roles in the etiology of pancreatic cancer. Exposure to carcinogens through cigarette smoking, diet, and occupational contact may increase the risk of pancreatic cancer. This hypothesis is supported by the experimental evidence that (1) the pancreas has the capacity to activate carcinogens; (2) DNA adducts are detected in pancreas tissue; and (3) genotoxic compounds might be involved, as suggested by the mutation spectra in pancreatic tumors. We hope, with advances in molecular biology and new methods of molecular epidemiological approach, to develop the tools for identifying high-risk individuals in whom this deadly disease can be prevented. An understanding of the etiological and molecular events leading to the development of pancreatic carcinoma may provide a basis for the development of effective strategies for the prevention, early diagnosis, and treatment of this disease.


Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Pancreatic Tissue Natl Cancer Inst 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Devesa SS, Blot WJ, Stone BJ, et al. Recent cancer trends in the United States. J Natl Cancer Inst. 1995;87:175–182.PubMedGoogle Scholar
  2. 2.
    Ahlgren JD. Epidemiology and risk factors in pancreatic cancer. Semin Oncol. 1996;23:241–250.PubMedGoogle Scholar
  3. 3.
    Niederhuber J, Brennan MF, Menck HR. The national cancer data base report on pancreatic cancer. Cancer. 1995;76:1671–1677.PubMedGoogle Scholar
  4. 4.
    Washaw LA, Fernandez Del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992;326:455–465.Google Scholar
  5. 5.
    Tominaga A, Kuroishi T. Epidemiology of pancreatic cancer. Semin Surg Oncol. 1998;15:3–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Anderson KE, Potter JD, Mack TM. Pancreatic cancer. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press;1996:725–771.Google Scholar
  7. 7.
    Gold EB, Goldin SB. Epidemiology of and risk factors for pancreatic cancer. Surg Oncol Clin N Am. 1998;7:67–91.PubMedGoogle Scholar
  8. 8.
    Lynch HT, Smyrk T, Kern SE, et al. Familial pancreatic cancer: a review. Semin Oncol. 1996;23:251–275.PubMedGoogle Scholar
  9. 9.
    Lumadue JA, Griffin CA, Osman M, et al. Familial pancreatic cancer and the genetics of pancreatic cancer. Panc Neopl. 1995;75:845–855.Google Scholar
  10. 10.
    Hruban RH, Petersen GM, Ha PK, et al. Genetics of pancreatic cancer. Surg Oncol Clin N Am. 1998;7:1–23.PubMedGoogle Scholar
  11. 11.
    Lowenfels AB, Maisonneuve P. Pancreatic cancer: development of a unifying etiologic concept. Ann N Y Acad Sci. 1999;880:191–200.CrossRefPubMedGoogle Scholar
  12. 12.
    Whitcomb DC, Applebaum S, Martin SP. Hereditary pancreatitis and pancreatic carcinoma. Ann N Y Acad Sci. 1999;880:201–209.CrossRefPubMedGoogle Scholar
  13. 13.
    Park JG, Park YJ, Wijnen JT, et al. Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing. Int J Cancer. 1999;82(4):516–519.CrossRefPubMedGoogle Scholar
  14. 14.
    Goggins M, Schutte M, Lu J, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996;56:5360–5364.PubMedGoogle Scholar
  15. 15.
    Lal G, Liu G, Schmocker B, et al. Genetic susceptibility is an important risk factor for pancreatic cancer. Proc Am Assoc Cancer Res. 1999;40:A3078.Google Scholar
  16. 16.
    Mack TM, Yu MC, Hanisch R, et al. Pancreas cancer and smoking, beverage consumption, and past medical history. J Natl Cancer Inst. 1986;76:49–60.PubMedGoogle Scholar
  17. 17.
    Silverman DT, Dunn JA, Hoover RN, et al. Cigarette smoking and pancreas cancer: a case-control study based on direct interview. J Natl Cancer Inst. 1994;86:1510–1516.PubMedGoogle Scholar
  18. 18.
    Muscat JE, Stellman SD, Hoffman D, et al. Smoking and pancreatic cancer in men and women. Cancer Epidemiol Biomarkers Prev. 1997;6:15–19.PubMedGoogle Scholar
  19. 19.
    Best EW. A Canadian Study of Smoking and Health. Ottawa: Department of National Health Welfare, 1996.Google Scholar
  20. 20.
    Floderus B, Cederlof R, Friberg L, et al. Smoking and mortality: a 21-year follow-up based on the Swedish Twin Registry. Int J Epidemiol. 1988;17(2):332–340.PubMedGoogle Scholar
  21. 21.
    Doll R. Cancers weakly related to smoking. Br Med Bull. 1996;52(1):35–49.PubMedGoogle Scholar
  22. 22.
    Hammond EC. Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr. 1966;19:126.Google Scholar
  23. 23.
    Hirayama T. Epidemiology of pancreatic cancer in Japan. Jpn J Clin Oncol. 1989;19(3):208–215.PubMedGoogle Scholar
  24. 24.
    Hirayama T. Smoking in relation to the death rates of 265,118 men and women in Japan: a report on five years of follow-up. In: American Cancer Society’s 14th Science Writers Seminar, Clearwater Beach, FL, 1972.Google Scholar
  25. 25.
    Kahn HA. The Dorn study of smoking and mortality among US veterans: report on 81/2; years of observation. In: Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. Washington, DC: US Public Health Service, 1996.Google Scholar
  26. 26.
    Shibata A, Mack TM, Pazanini-Hill A, et al. A prospective study of pancreatic cancer in the elderly. Int J Cancer. 1994;58(1):46–49.PubMedGoogle Scholar
  27. 27.
    Fernandez E, Vecchia CL, Decarli A. Attributable risks for pancreatic cancer in Northern Italy. Cancer Epidemiol Biomarkers Prev. 1996;5:23–27.PubMedGoogle Scholar
  28. 28.
    Fraumeni JF. Cancers of the pancreas and biliary tract: epidemiological considerations. Cancer Res. 1975;35:3437–3446.PubMedGoogle Scholar
  29. 29.
    Neugut AI, Ahsan H, Robinson E. Pancreas cancer as second primary malignancy. A population-based study. Cancer. 1995;76:589–592.PubMedGoogle Scholar
  30. 30.
    Ji BT, Chow WH, Gridley G, et al. Dietary factors and the risk of pancreatic cancer: a case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 1995;4:885–893.PubMedGoogle Scholar
  31. 31.
    Soler M, Chatenoud L, La Vecchia C, et al. Diet, alcohol, coffee and pancreatic cancer: final results from an Italian study. Eur J Cancer Prev. 1998;7(6):455–460.PubMedGoogle Scholar
  32. 32.
    Stephens FO. The increased incidence of cancer of the pancreas: is there a missing dietary factor? Can it be reversed? Aust N Z J Surg. 1999;69(5):331–335.CrossRefPubMedGoogle Scholar
  33. 33.
    Silverman DT, Swanson CA, Gridley G, et al. Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1998;90:1710–1719.CrossRefPubMedGoogle Scholar
  34. 34.
    Carroll KK. Obesity as a risk factor for certain types of cancer. Lipids. 1998;33(11):1055–1059.PubMedGoogle Scholar
  35. 35.
    Ghadirian P, Baillargeon J, Simard A, et al. Food habits and pancreatic cancer: a case-control study of the francophone community in Montreal, Canada. Cancer Epidemiol Biomarkers Prev. 1995;4:895–899.PubMedGoogle Scholar
  36. 36.
    Knekt P, Steineck G, Jarvinen R, et al. Intake of fried meat and risk of cancer: a follow-up study in Finland. Int J Cancer. 1994;59(6):756–760.PubMedGoogle Scholar
  37. 37.
    Ohba S, Nishi M, Miyake H. Eating habits and pancreatic cancer. Int J Pancreatol. 1996;20:37–42.PubMedGoogle Scholar
  38. 38.
    Burney PG, Comstock GW, Morris JS. Serological precursors of cancer serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr. 1989;49:895–900.PubMedGoogle Scholar
  39. 39.
    Stolzenberg-Solomon RZ, Albanes D, Nieto FJ, et al. Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. J Natl Cancer Inst. 1999;91(6):535–541.CrossRefPubMedGoogle Scholar
  40. 40.
    Durbec JP, Chevillotte G, Bidart JM, et al. Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study. Br J Cancer. 1983;47:463–470.PubMedGoogle Scholar
  41. 41.
    Heuch I, Kvale G, Jacobsen BK, et al. Use of alcohol, tobacco and coffee, and risk of pancreatic cancer. Br J Cancer. 1983;48:637–643.PubMedGoogle Scholar
  42. 42.
    Silverman DT, Brown LM, Hoover RN, et al. Alcohol and pancreatic cancer in blacks and whites in the United States. Cancer Res. 1995;55:4899–4905.PubMedGoogle Scholar
  43. 43.
    Bouchardy C, Clavel F, La Vecchia C, et al. Alcohol, beer and cancer of the pancreas. Int J Cancer. 1990;45:842–846.PubMedGoogle Scholar
  44. 44.
    Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, et al. Lifetime consumption of alcoholic beverages, tea, and coffee and exocrine carcinoma of the pancreas: a population-based case-control study in the Netherlands. Int J Cancer. 1992;50:514–522.PubMedGoogle Scholar
  45. 45.
    Clavel F, Benhamou E, Auquier A, et al. Coffee, alcohol, smoking and cancer of the pancreas: a case-control study. Int J Cancer. 1989;43:17–21.PubMedGoogle Scholar
  46. 46.
    Falk RT, Pickle LW, Fontham ET, et al. Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. Am J Epidemiol. 1988;28:324–326.Google Scholar
  47. 47.
    Farrow DC, Davis S. Diet and the risk of pancreatic cancer in men. Am J Epidemiol. 1990;132:423–431.PubMedGoogle Scholar
  48. 48.
    Mizuno S, Watanabe S, Nakamura K, et al. A multi-institute case-control study on the risk factors of developing pancreatic cancer. Jpn J Clin Oncol. 1992;22:286–291.PubMedGoogle Scholar
  49. 49.
    Zatonski WA, Boyle P, Przewozniak K, et al. Cigarette smoking, alcohol, tea, and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland. Int J Cancer. 1993;53:601–607.PubMedGoogle Scholar
  50. 50.
    Longnecker MP, Enger MS. Epidemiologic data on alcoholic beverage consumption and risk of cancer. Clin Chim Acta. 1996;246:121–141.CrossRefPubMedGoogle Scholar
  51. 51.
    Thomas DB. Alcohol as a cause of cancer. Environ Health Perspect. 1995;103(suppl 8):153–160.PubMedGoogle Scholar
  52. 52.
    Norell S, Ahlbom A, Olin R, et al. Occupational factors and pancreatic cancer. Br J Ind Med. 1986;43(11):775–778.PubMedGoogle Scholar
  53. 53.
    Kauppinen T, Partanen T, Degerth R, et al. Pancreatic cancer and occupational exposures. Epidemiology. 1995;6:498–502.PubMedGoogle Scholar
  54. 54.
    Ji BT, Silverman DT, Dosemeci M, et al. Occupation and pancreatic cancer risk in Shanghai, China. Am J Ind Med. 1999;35(1):76–81.CrossRefPubMedGoogle Scholar
  55. 55.
    Park RM, Mirer FE. A survey of mortality at two automotive engine manufacturing plants. Am J Ind Med. 1996;30:664–673.PubMedGoogle Scholar
  56. 56.
    Bardin JA, Eisen EA, Tolbert PE, 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):240–247.CrossRefPubMedGoogle Scholar
  57. 57.
    Garabrani DH, Held J, Langholz B, et al. DDT and related compounds and risk of pancreatic cancer. J Natl Cancer Inst. 1992;84:764–771.Google Scholar
  58. 58.
    Fryzek J, Garabrant DH, Harlow SD, et al. A case-control study of self-reported exposures to pesticides and pancreas cancer in Southern Michigan. Int J Cancer. 1997;72:62–67.CrossRefPubMedGoogle Scholar
  59. 59.
    Jaga K, Brosius D. Pesticide exposure: human cancers on the horizon. Rev Environ Health. 1999;14(1):39–50.PubMedGoogle Scholar
  60. 60.
    Kernan GJ, Ji BT, Dosemeci M, et al. 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):260–270.CrossRefPubMedGoogle Scholar
  61. 61.
    Anttila A, Pukkala E, Riala R, et al. Cancer incidence among Finnish workers exposed to aromatic hydrocarbons. Int Arch Occup Environ Health. 1998;71:187–193.PubMedGoogle Scholar
  62. 62.
    Jarvholm B, Sanden A. Lung cancer and mesothelioma in the pleura and peritoneum among Swedish insulation workers. Occup Environ Med. 1998;55(11):766–770.PubMedGoogle Scholar
  63. 63.
    Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, et al. Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in the Netherlands. Int J Cancer. 1992;52:17–23.PubMedGoogle Scholar
  64. 64.
    La Vecchia C, Negri E, D’Avanzo B, et al. Medical history, diet and pancreatic cancer. Oncology. 1990;47(6):463–466.PubMedGoogle Scholar
  65. 65.
    Lowenfels AB, Maisonneuve P, Gavallini G, et al. Pancreatitis and the risk of pancreatic cancer. N Eng J Med. 1993;328:1433–1437.Google Scholar
  66. 66.
    Ekbom A, McLaughlin JK, Nyren O, et al. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst. 1994;86:625–627.PubMedGoogle Scholar
  67. 67.
    Talamini G, Falconi M, Bassi C, et al. Incidence of cancer in the course of chronic pancreatitis. Am J Gastrenterol. 1999;94(5):1253–1260.Google Scholar
  68. 68.
    Hecht SS. Approaches to cancer prevention based on an understanding of N-nitrosoamine carcinogenesis. Proc Soc Exp Biol Med. 1997;216(2):181–191.PubMedGoogle Scholar
  69. 69.
    Wynder EL/, Mabuchi K, Marruchi N, et al. Epidemiology of cancer of the pancreas. J Natl Cancer Inst. 1973;50:645–667.PubMedGoogle Scholar
  70. 70.
    Morgan RR, Wormsley K. Progress report: cancer of the pancreas. Gut. 1977;18:580–596.PubMedGoogle Scholar
  71. 71.
    Harris CC, Autrup H, Stoner G, et al. Metabolism of benzo[a]pyrene and 7,12-dimethyl-benz[a]anthracene in cultured human bronchus and pancreatic duct. Cancer Res. 1977;37:3349–3355.PubMedGoogle Scholar
  72. 72.
    Foster JR, Idle JR, Hardwick JP, et al. Induction of drug-metabolizing enzymes in human pancreatic cancer and chronic pancreatitis. J Pathol. 1993;169:457–463.CrossRefPubMedGoogle Scholar
  73. 73.
    Wacke R, Kirchner A, Prall F, et al. Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis. Pancreas. 1998;16:521–528.CrossRefPubMedGoogle Scholar
  74. 74.
    Chassagne P, Daujat M, Maurel P, et al. Cytochromes P-450 1A1 and 2E1 are present in human pancreas. Evidence by molecular biology. Gastroenterology. 1995;108:A348.Google Scholar
  75. 75.
    Anderson KE, Hammons GJ, Kadlubar FK, et al. Metabolic activation of aromatic amines by human pancreas. Carcinogenesis. 1997;18:1085–1092.CrossRefPubMedGoogle Scholar
  76. 76.
    Collier JD, Bennett MK, Hall A, et al. Expression of glutathione S-transferases in normal and malignant pancreas: an immunohistochemical study. Gut. 1994;35:266–269.PubMedGoogle Scholar
  77. 77.
    Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epiodemiol Biomarkers Prev. 1977;6:733–743.Google Scholar
  78. 78.
    Coles BF, Anderson KE, Doerge DR, et al. Quantitative analysis of interindividual variation of glutathione S-transferase expression in human pancreas and the ambiguity of correlating genotype with phenotype. Cancer Res. 2000;60:573–579.PubMedGoogle Scholar
  79. 79.
    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;12:128–136.PubMedGoogle Scholar
  80. 80.
    Bartsch H, Malaveille C, Lowenfels AB, et al. 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):215–223.PubMedGoogle Scholar
  81. 81.
    Kaderlik KR, Minchin RF, Mulder GJ, et al. Metabolic activation pathway for the formation of DNA adducts of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-β]pyridine (PhIP) in rat extrahepatic tissues. Carcinogenesis. 1994;15:1703–1709.PubMedGoogle Scholar
  82. 82.
    Kadlubar FF, Kaderlik KR, Mulder GJ, et al. Metabolic activation and DNA detection of PhIP in dogs, rats, and humans in relation to urinary bladder and colon carcinogenesis. In Adamson RH, et al, eds, Heterocyclic Amines and Cooked Foods: Possible Human Carcinogens. Princeton, NJ: Scientific Publishing Co, Inc; 1995:207–213.Google Scholar
  83. 83.
    Cuzick J, Routledge MN, Jenkins D, et al. DNA adducts in different tissues of smokers and nonsmokers. Int J Cancer. 1990;45(4):673–678.PubMedGoogle Scholar
  84. 84.
    Wang MY, Abbruzzese JL, Friess H, et al. DNA adducts in human pancreatic tissues and their potential role in carcinogenesis. Cancer Res. 1998;58:38–41.PubMedGoogle Scholar
  85. 85.
    Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915–7922.PubMedGoogle Scholar
  86. 86.
    Guyton KZ, Kensler TW. Oxidative mechanisms in carcinogenesis. Br Med Bull. 1993;49:523–544.PubMedGoogle Scholar
  87. 87.
    Schoenberg MH, Buchler M, Gaspar M, et al. The involvement of oxygen radicals in acute pancreatitis. Gut. 1990;31:1138–1143.PubMedGoogle Scholar
  88. 88.
    Schoenberg MH, Buchler M, Pietrzyk C, et al. Lipid peroxidation and glutathione metabolism in chronic pancreatitis. Pancreas. 1995;10:36–43.CrossRefPubMedGoogle Scholar
  89. 89.
    Wereszcynska-Siemiatkowska U, Dabrowski A, Jedynak M, et al. Oxidative stress as an early prognostic factor in acute pancreatitis (AP): its correlation with serum phospholipase A2 (PLA2) and plasma polymorphonuclear elastase (PMN-E) in different-severity forms of human AP. Pancreas. 1998;17:163–168.Google Scholar
  90. 90.
    Nair J, Link KH, Beger HG, et al. Detection of elevated lipid peroxidation-induced etheno-DNA adducts in human chronic pancreatitis. Proc Am Assoc Cancer Res. 1999;40:A4256.Google Scholar
  91. 91.
    Thompson PA, Seyedi F, Lang NP, et al. Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype. Mutat Res. 1999;424(1–2):263–274.PubMedGoogle Scholar
  92. 92.
    Kadlubar FF, Anderson KE, Häussermann S, et al. Comparison of DNA adduct levels associated with oxidative stress in human pancreas. Mutat Res. 1998;405(2):125–133.PubMedGoogle Scholar
  93. 93.
    Marnett LJ. Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res. 1999;424(1–2):83–95.PubMedGoogle Scholar
  94. 94.
    Lau SS, Peters MMCG, Kleiner HE, et al. Biological reactive intermediates V. In: Snyder RR, et al, eds, Basic Mechanistic Research in Toxicology and Human Health Risk Assessment. New York: Plenum Press; 1996:267–273.Google Scholar
  95. 95.
    Li D, Friess H, Abbruzzese JL. 8-hydroxyguanine and other DNA damage in human pancreatic cancer. Proc Am Assoc Cancer Res. 1999;40:A4425.Google Scholar
  96. 96.
    Pegg AE. Methylation of the O6-position of guanine in DNA is the most likely initiating event in carcinogenesis by methylating agents. Cancer Invest. 1984;2:223–231.PubMedGoogle Scholar
  97. 97.
    Greenblatt MS, Bennett WP, Hollstein M, et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54:4855–4878.PubMedGoogle Scholar
  98. 98.
    Hussain SP, Harris CC. Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res. 1998;58:4023–4037.PubMedGoogle Scholar
  99. 99.
    Blanck HM, Tolbert PE, Hoppin JA. Patterns of genetic alterations in pancreatic cancer: a pooled analysis. Environ Mol Mutagen. 1999;33(2):111–122.CrossRefPubMedGoogle Scholar
  100. 100.
    Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549–554.CrossRefPubMedGoogle Scholar
  101. 101.
    Banerjee SK, Makdisi WF, Weston AP, et al. A two-step enriched-nested PCR technique enhances sensitivity for detection of codon 12 K-ras mutations in pancreatic adenocarcinoma. Pancreas. 1997;15:16–24.CrossRefPubMedGoogle Scholar
  102. 102.
    Moskaluk CA, Hruban RH, Kern SE. p16 and Kras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997;57:2140–2143.PubMedGoogle Scholar
  103. 103.
    Rall CJN, Yan YX, Graeme-Cook F, et al. Ki-ras and p53 mutations in pancreatic ductal adenocarcinoma. Pancreas. 1996;12:10–17.CrossRefPubMedGoogle Scholar
  104. 104.
    Scarpa A, Capelli P, Villanueva A, et al. Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences. Int J Cancer. 1994;57:167–171.PubMedGoogle Scholar
  105. 105.
    Berrozpe G, Schaeffer J, Peinado MA, et al. Comparative analysis of mutations in the p53 and K-ras genes in pancreatic cancer. Int J Cancer. 1994;58:185–191.PubMedGoogle Scholar
  106. 106.
    Cerny WL, Mangold KA, Scarpelli DG. K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster. Cancer Res. 1992;52:4507–4513.PubMedGoogle Scholar
  107. 107.
    Schaeffer BK, Glasner S, Kuhlmann ET, et al. Mutated c-K-ras in small pancreatic adenocarcinomas. Pancreas. 1994;9:161–165.CrossRefPubMedGoogle Scholar
  108. 108.
    Tada M, Omata M, Kawai S, et al. Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res. 1993;53:2472–2474.PubMedGoogle Scholar
  109. 109.
    Caldas C, Hahn SA, Hruban RH, et al. Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res. 1994;54:3568–3573.PubMedGoogle Scholar
  110. 110.
    Abbruzzese JL, Evans DB, Raijman I, et al. Detection of mutated c-Ki-ras in the bile of patients with pancreatic cancer. Anticancer Res. 1997;17:795–801.PubMedGoogle Scholar
  111. 111.
    Iguchi H, Sugano K, Fukayama N, et al. Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with pancreatic cancer. Gastroenterology. 1996;110:221–226.CrossRefPubMedGoogle Scholar
  112. 112.
    Terhune PG, Phifer DM, Tosteson TD, et al. K-ras mutation in focal proliferative lesions of human pancreas. Cancer Epidemiol Biomarkers Prev. 1998;7:515–521.PubMedGoogle Scholar
  113. 113.
    Malats N, Porta M, Corominas JM, et al. Ki-ras mutations in exocrine pancreatic cancer: association with clinico-pathological characteristics and with tobacco and alcohol consumption. Int J Cancer. 1997;70:661–667.CrossRefPubMedGoogle Scholar
  114. 114.
    Hruban RH, van Mansfield ADM, Offerhaus GJA, et al. K-ras oncogene activation in adenocarcinoma of the human pancreas: a study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol. 1993;143:545–554.PubMedGoogle Scholar
  115. 115.
    Nagata Y, Abe M, Motoshima K, et al. Frequent glycine-to-aspartic acid mutations at codon 12 of c-Ki-ras gene in human pancreatic cancer in Japanese. Jpn J Cancer Res. 1990;81:135–140.PubMedGoogle Scholar
  116. 116.
    Berger DH, Chang H, Wood M, et al. Mutational activation of K-ras in non-neoplastic exocrine pancreatic lesions in relation to cigarette smoking status. Cancer. 1999;85(2):326–329.CrossRefPubMedGoogle Scholar
  117. 117.
    Cooper GM. Role of oncogenes and tumor suppressor genes in the pathogenesis of neoplasms. In: Oncogene. Boston: Jones-Bartlett Publishers; 1990:141–162.Google Scholar
  118. 118.
    Sugio K, Gazdar AF, Albores-Saavedra J, et al. High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl) amine in the pancreas of female Syrian hamsters. Carcinogenesis. 1996;17:303–309.PubMedGoogle Scholar
  119. 119.
    Cooper CA, Carey FA, Bubb VJ, et al. The pattern of K-ras mutation in pulmonary adenocarcinoma defines a new pathway of tumor development in the human lung. J Pathol. 1997;181:401–404.CrossRefPubMedGoogle Scholar
  120. 120.
    Ringborg U. Alcohol and risk of cancer. Alcohol Clin Exp Res. 1998;22(7 suppl):323S–328S.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 2002

Authors and Affiliations

  • Donghui Li

There are no affiliations available

Personalised recommendations