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Epidemiology and nonfamilial risk factors for exocrine pancreatic cancer

Authors
Carlos Fernandez-del Castillo, MD
Ramon E Jimenez, MD
Section Editor
Kenneth K Tanabe, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Surgical resection is the only potentially curative treatment for exocrine pancreatic cancer, but because of the late presentation of the disease, only 15 to 20 percent of patients are candidates for pancreatectomy. Furthermore, the prognosis of pancreatic cancer is poor even in those with potentially resectable disease. The five-year survival following pancreaticoduodenectomy is only about 25 to 30 percent for node-negative and 10 percent for node-positive tumors. (See "Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis".)

The nonfamilial risk factors for carcinoma of the exocrine pancreas will be reviewed here. Familial risk factors and screening for pancreatic cancer in high-risk individuals who have a family history of the disease, as well as the pathology, molecular pathogenesis, clinical manifestations, and diagnosis of this disorder are discussed separately. (See "Familial risk factors for pancreatic cancer and screening of high-risk patients" and "Pathology of exocrine pancreatic neoplasms" and "Molecular pathogenesis of exocrine pancreatic cancer" and "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer".)

EPIDEMIOLOGY

In the United States, approximately 53,070 patients are diagnosed with cancer of the exocrine pancreas annually, and almost all are expected to die from the disease [1]. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States among both men and women. The majority of these tumors (85 percent) are adenocarcinomas arising from the ductal epithelium. (See "Pathology of exocrine pancreatic neoplasms".)

Worldwide, pancreatic cancer is the eighth leading cause of cancer deaths in men (138,100 deaths annually) and the ninth in women (127,900 deaths annually) [2]. In general, pancreatic cancer affects more individuals inhabiting the Western/industrialized parts of the world; the highest incidence is reported among Maoris in New Zealand, native Hawaiians, and Black American populations, while people living in India and Nigeria have the lowest reported incidence [3,4].

The disease is rare before the age of 45, but the incidence rises sharply thereafter. Incidence and death rates vary by sex and race [5]. The incidence is greater in males than females (male-to-female ratio 1.3:1) and in blacks than in whites (14.8 per 100,000 in black males compared with 8.8 per 100,000 in the general population) [6]. However, more recent data suggest that these racial differences may be diminishing [7].

                

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Literature review current through: Nov 2016. | This topic last updated: Fri Sep 09 00:00:00 GMT+00:00 2016.
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References
Top
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7.
  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.
  3. Boyle P, Hsieh CC, Maisonneuve P, et al. Epidemiology of pancreas cancer (1988). Int J Pancreatol 1989; 5:327.
  4. Hariharan D, Saied A, Kocher HM. Analysis of mortality rates for pancreatic cancer across the world. HPB (Oxford) 2008; 10:58.
  5. Zhang J, Dhakal I, Ning B, Kesteloot H. Patterns and trends of pancreatic cancer mortality rates in Arkansas, 1969-2002: a comparison with the US population. Eur J Cancer Prev 2008; 17:18.
  6. Ries LA, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review, 1973-1996. National Cancer Institute, Bethesda, MD 2000.
  7. Ma J, Siegel R, Jemal A. Pancreatic cancer death rates by race among US men and women, 1970-2009. J Natl Cancer Inst 2013; 105:1694.
  8. Klein AP, Hruban RH, Brune KA, et al. Familial pancreatic cancer. Cancer J 2001; 7:266.
  9. Olson SH, Kurtz RC. Epidemiology of pancreatic cancer and the role of family history. J Surg Oncol 2013; 107:1.
  10. Wolpin BM, Chan AT, Hartge P, et al. ABO blood group and the risk of pancreatic cancer. J Natl Cancer Inst 2009; 101:424.
  11. Annese V, Minervini M, Gabbrielli A, et al. ABO blood groups and cancer of the pancreas. Int J Pancreatol 1990; 6:81.
  12. Risch HA, Yu H, Lu L, Kidd MS. ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: a case-control study. J Natl Cancer Inst 2010; 102:502.
  13. Wolpin BM, Kraft P, Gross M, et al. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium. Cancer Res 2010; 70:1015.
  14. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009; 41:986.
  15. Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 1993; 328:1433.
  16. Ekbom A, McLaughlin JK, Karlsson BM, et al. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst 1994; 86:625.
  17. Duell EJ, Lucenteforte E, Olson SH, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23:2964.
  18. Bang UC, Benfield T, Hyldstrup L, et al. Mortality, cancer, and comorbidities associated with chronic pancreatitis: a Danish nationwide matched-cohort study. Gastroenterology 2014; 146:989.
  19. Liou GY, Döppler H, Necela B, et al. Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs. J Cell Biol 2013; 202:563.
  20. Huxley R, Ansary-Moghaddam A, Berrington de González A, et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92:2076.
  21. Inoue M, Iwasaki M, Otani T, et al. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 2006; 166:1871.
  22. Chow WH, Gridley G, Nyrén O, et al. Risk of pancreatic cancer following diabetes mellitus: a nationwide cohort study in Sweden. J Natl Cancer Inst 1995; 87:930.
  23. Calle EE, Murphy TK, Rodriguez C, et al. Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control 1998; 9:403.
  24. Wideroff L, Gridley G, Mellemkjaer L, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 1997; 89:1360.
  25. Jee SH, Ohrr H, Sull JW, et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005; 293:194.
  26. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas 2013; 42:198.
  27. Bosetti C, Rosato V, Li D, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol 2014; 25:2065.
  28. 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; 21:2453.
  29. Gullo L, Pezzilli R, Morselli-Labate AM, Italian Pancreatic Cancer Study Group. Diabetes and the risk of pancreatic cancer. N Engl J Med 1994; 331:81.
  30. Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008; 134:95.
  31. Pannala R, Leirness JB, Bamlet WR, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology 2008; 134:981.
  32. Wong HK, Tang F, Cheung TT, Cheung BM. Adrenomedullin and diabetes. World J Diabetes 2014; 5:364.
  33. Javeed N, Sagar G, Dutta SK, et al. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction. Clin Cancer Res 2015; 21:1722.
  34. Gapstur SM, Gann PH, Lowe W, et al. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000; 283:2552.
  35. Stolzenberg-Solomon RZ, Graubard BI, Chari S, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 2005; 294:2872.
  36. Michaud DS, Liu S, Giovannucci E, et al. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst 2002; 94:1293.
  37. Wolpin BM, Bao Y, Qian ZR, et al. Hyperglycemia, insulin resistance, impaired pancreatic β-cell function, and risk of pancreatic cancer. J Natl Cancer Inst 2013; 105:1027.
  38. Bao Y, Giovannucci EL, Kraft P, et al. A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst 2013; 105:95.
  39. Pelaez-Luna M, Takahashi N, Fletcher JG, Chari ST. Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis. Am J Gastroenterol 2007; 102:2157.
  40. Tanaka M. Controversies in the management of pancreatic IPMN. Nat Rev Gastroenterol Hepatol 2011; 8:56.
  41. Rebours V, Lévy P, Ruszniewski P. An overview of hereditary pancreatitis. Dig Liver Dis 2012; 44:8.
  42. Lowenfels AB, Maisonneuve P, Whitcomb DC. Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group. Med Clin North Am 2000; 84:565.
  43. Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol 2006; 20:197.
  44. Mack TM, Yu MC, Hanisch R, Henderson BE. Pancreas cancer and smoking, beverage consumption, and past medical history. J Natl Cancer Inst 1986; 76:49.
  45. Farrow DC, Davis S. Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee. Int J Cancer 1990; 45:816.
  46. Ghadirian P, Simard A, Baillargeon J. Tobacco, alcohol, and coffee and cancer of the pancreas. A population-based, case-control study in Quebec, Canada. Cancer 1991; 67:2664.
  47. Lynch SM, Vrieling A, Lubin JH, et al. Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Am J Epidemiol 2009; 170:403.
  48. Nöthlings U, Wilkens LR, Murphy SP, et al. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 2005; 97:1458.
  49. Silverman DT, Dunn JA, Hoover RN, et al. Cigarette smoking and pancreas cancer: a case-control study based on direct interviews. J Natl Cancer Inst 1994; 86:1510.
  50. Duell EJ, Holly EA, Bracci PM, et al. A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J Natl Cancer Inst 2002; 94:297.
  51. Bosetti C, Lucenteforte E, Silverman DT, et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 2012; 23:1880.
  52. Fuchs CS, Colditz GA, Stampfer MJ, et al. A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch Intern Med 1996; 156:2255.
  53. Michaud DS, Giovannucci E, Willett WC, et al. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 2001; 286:921.
  54. Stolzenberg-Solomon RZ, Adams K, Leitzmann M, et al. Adiposity, physical activity, and pancreatic cancer in the National Institutes of Health-AARP Diet and Health Cohort. Am J Epidemiol 2008; 167:586.
  55. Luo J, Margolis KL, Adami HO, et al. Obesity and risk of pancreatic cancer among postmenopausal women: the Women's Health Initiative (United States). Br J Cancer 2008; 99:527.
  56. Li D, Morris JS, Liu J, et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 2009; 301:2553.
  57. O'Rorke MA, Cantwell MM, Cardwell CR, et al. Can physical activity modulate pancreatic cancer risk? a systematic review and meta-analysis. Int J Cancer 2010; 126:2957.
  58. Arslan AA, Helzlsouer KJ, Kooperberg C, et al. Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch Intern Med 2010; 170:791.
  59. Aune D, Greenwood DC, Chan DS, 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; 23:843.
  60. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med 2016; 375:794.
  61. Yuan C, Bao Y, Wu C, et al. Prediagnostic body mass index and pancreatic cancer survival. J Clin Oncol 2013; 31:4229.
  62. 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.
  63. Thiébaut AC, Jiao L, Silverman DT, et al. Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. J Natl Cancer Inst 2009; 101:1001.
  64. Larsson SC, Wolk A. Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. Br J Cancer 2012; 106:603.
  65. Michaud DS, Giovannucci E, Willett WC, et al. Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol 2003; 157:1115.
  66. Michaud DS, Skinner HG, Wu K, et al. Dietary patterns and pancreatic cancer risk in men and women. J Natl Cancer Inst 2005; 97:518.
  67. Rohrmann S, Linseisen J, Nöthlings U, 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; 132:617.
  68. Norell SE, Ahlbom A, Erwald R, et al. Diet and pancreatic cancer: a case-control study. Am J Epidemiol 1986; 124:894.
  69. Howe GR, Jain M, Miller AB. Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study. Int J Cancer 1990; 45:604.
  70. Gold EB, Gordis L, Diener MD, et al. Diet and other risk factors for cancer of the pancreas. Cancer 1985; 55:460.
  71. 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; 11:915.
  72. Arem H, Reedy J, Sampson J, et al. The Healthy Eating Index 2005 and risk for pancreatic cancer in the NIH-AARP study. J Natl Cancer Inst 2013; 105:1298.
  73. Burney PG, Comstock GW, Morris JS. Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr 1989; 49:895.
  74. Han X, Li J, Brasky TM, et al. Antioxidant intake and pancreatic cancer risk: the Vitamins and Lifestyle (VITAL) Study. Cancer 2013; 119:1314.
  75. Nkondjock A, Ghadirian P, Johnson KC, et al. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr 2005; 135:592.
  76. Michaud DS, Vrieling A, Jiao L, et al. Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan). Cancer Causes Control 2010; 21:1213.
  77. Lucenteforte E, La Vecchia C, Silverman D, et al. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23:374.
  78. Turati F, Galeone C, Edefonti V, et al. A meta-analysis of coffee consumption and pancreatic cancer. Ann Oncol 2012; 23:311.
  79. Anderson KE, Johnson TW, Lazovich D, Folsom AR. Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J Natl Cancer Inst 2002; 94:1168.
  80. Bradley MC, Hughes CM, Cantwell MM, et al. Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case-control study. Br J Cancer 2010; 102:1415.
  81. Langman MJ, Cheng KK, Gilman EA, Lancashire RJ. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 2000; 320:1642.
  82. Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 1994; 5:138.
  83. Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85:307.
  84. Schernhammer ES, Kang JH, Chan AT, et al. A prospective study of aspirin use and the risk of pancreatic cancer in women. J Natl Cancer Inst 2004; 96:22.
  85. Jacobs EJ, Connell CJ, Rodriguez C, et al. Aspirin use and pancreatic cancer mortality in a large United States cohort. J Natl Cancer Inst 2004; 96:524.
  86. 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.
  87. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294:47.
  88. Streicher SA, Yu H, Lu L, et al. Case-control study of aspirin use and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2014; 23:1254.
  89. Hassan MM, Li D, El-Deeb AS, et al. Association between hepatitis B virus and pancreatic cancer. J Clin Oncol 2008; 26:4557.