Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors

Abstract

Pancreatic cancer is a leading cause of cancer death worldwide and its global burden has more than doubled over the past 25 years. The highest incidence regions for pancreatic cancer include North America, Europe and Australia, and although much of this increase is due to ageing worldwide populations, there are key modifiable risk factors for pancreatic cancer such as cigarette smoking, obesity, diabetes and alcohol intake. The prevalence of these risk factors is increasing in many global regions, resulting in increasing age-adjusted incidence rates for pancreatic cancer, but the relative contribution from these risk factors varies globally due to variation in the underlying prevalence and prevention strategies. Inherited genetic factors, although not directly modifiable, are an important component of pancreatic cancer risk, and include pathogenic variants in hereditary cancer genes, genes associated with hereditary pancreatitis, as well as common variants identified in genome-wide association studies. Identification of the genetic changes that underlie pancreatic cancer not only provides insight into the aetiology of this cancer but also provides an opportunity to guide early detection strategies. The goal of this Review is to provide an up-to-date overview of the established modifiable and inherited risk factors for pancreatic cancer.

Key points

  • Smoking continues to be a leading cause of pancreatic cancer worldwide.

  • Increasing rates of diabetes and obesity will probably result in increased rates of pancreatic cancer.

  • Growing evidence indicates that high alcohol intake contributes to pancreatic cancer risk.

  • Knowledge of inherited genetic factors in pancreatic cancer continues to grow and probably explains 22–33% of pancreatic cancer risk.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Incidence of pancreatic cancer.

References

  1. 1.

    GBD 2017 Pancreatic Cancer Collaborators. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 4, 934–947 (2019).

    Google Scholar 

  2. 2.

    He, W., Goodkind, D. & Kowal, P. An Aging World: 2015. US Census Bureau Report Number P95/16-1 (US Government Publishing Office, 2016).

  3. 3.

    Klein, A. P. Pancreatic cancer: a growing burden. Lancet Gastroenterol. Hepatol. 4, 895–896 (2019).

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Ferlay, J. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer 144, 1941–1953 (2019).

    CAS  PubMed  Google Scholar 

  5. 5.

    International Agency for Research on Cancer. Cancer Today https://gco.iarc.fr/today/online-analysis-map?v=2020&mode=population&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=13&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=10&group_cancer=1&include_nmsc=1&include_nmsc_other=1&projection=natural-earth&color_palette=default&map_scale=quantile&map_nb_colors=5&continent=0&show_ranking=0&rotate=%255B10%252C0%255D (2020).

  6. 6.

    Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).

    PubMed  Google Scholar 

  7. 7.

    Silverman, D. T. et al. Why do Black Americans have a higher risk of pancreatic cancer than White Americans? Epidemiology 14, 45–54 (2003).

    PubMed  Google Scholar 

  8. 8.

    Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7–30 (2020).

    PubMed  Google Scholar 

  9. 9.

    Jemal, A. et al. Cancer statistics, 2006. CA Cancer J. Clin 56, 106–130 (2006).

    PubMed  Google Scholar 

  10. 10.

    He, J. et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB 16, 83–90 (2014).

    PubMed  Google Scholar 

  11. 11.

    Blackford, A. L., Canto, M. I., Klein, A. P., Hruban, R. H. & Goggins, M. Recent trends in the incidence and survival of stage 1A pancreatic cancer: a Surveillance, Epidemiology, and End Results analysis. J. Natl Cancer Inst. 112, 1162–1169 (2020).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Wood, L. D. & Hruban, R. H. Pathology and molecular genetics of pancreatic neoplasms. Cancer J. 18, 492–501 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Iodice, S., Gandini, S., Maisonneuve, P. & Lowenfels, A. B. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch. Surg. 393, 535–545 (2008).

    PubMed  Google Scholar 

  14. 14.

    Bosetti, C. et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann. Oncol. 23, 1880–1888 (2012).

    CAS  PubMed  Google Scholar 

  15. 15.

    Lynch, S. M. et al. Cigarette smoking and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium. Am. J. Epidemiol. 170, 403–413 (2009).

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Koyanagi, Y. N. et al. Smoking and pancreatic cancer incidence: a pooled analysis of 10 population-based cohort studies in Japan. Cancer Epidemiol. Biomarkers Prev. 28, 1370–1378 (2019).

    PubMed  Google Scholar 

  17. 17.

    Bao, Y., Giovannucci, E., Fuchs, C. S. & Michaud, D. S. Passive smoking and pancreatic cancer in women: a prospective cohort study. Cancer Epidemiol. Biomarkers Prev. 18, 2292–2296 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Zhou, J., Wellenius, G. A. & Michaud, D. S. Environmental tobacco smoke and the risk of pancreatic cancer among non-smokers: a meta-analysis. Occup. Env. Med. 69, 853–857 (2012).

    Google Scholar 

  19. 19.

    Bertuccio, P. et al. Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann. Oncol. 22, 1420–1426 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Araghi, M. et al. Use of moist oral snuff (snus) and pancreatic cancer: pooled analysis of nine prospective observational studies. Int. J. Cancer 141, 687–693 (2017).

    CAS  PubMed  Google Scholar 

  21. 21.

    Tranah, G. J., Holly, E. A., Wang, F. & Bracci, P. M. 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 11, 138 (2011).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Marcon, A. et al. Trends in smoking initiation in Europe over 40 years: a retrospective cohort study. PLoS ONE 13, e0201881 (2018).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Yang, J. J. et al. Tobacco smoking and mortality in Asia: a pooled meta-analysis. JAMA Netw. Open 2, e191474 (2019).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Maisonneuve, P. & Lowenfels, A. B. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int. J. Epidemiol. 44, 186–198 (2015).

    PubMed  Google Scholar 

  25. 25.

    Rosato, V. et al. Population attributable risk for pancreatic cancer in Northern Italy. Pancreas 44, 216–220 (2015).

    PubMed  Google Scholar 

  26. 26.

    Everhart, J. & Wright, D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 273, 1605–1609 (1995).

    CAS  PubMed  Google Scholar 

  27. 27.

    Huxley, R., Ansary-Moghaddam, A., Berrington de Gonzalez, A., Barzi, F. & Woodward, M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br. J. Cancer 92, 2076–2083 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Bosetti, C. et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann. Oncol. 25, 2065–2072 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Elena, J. W. et al. Diabetes and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium. Cancer Causes Control. 24, 13–25 (2013).

    PubMed  Google Scholar 

  30. 30.

    Li, D. et al. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control. 22, 189–197 (2011).

    CAS  PubMed  Google Scholar 

  31. 31.

    Chari, S. T. et al. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 129, 504–511 (2005).

    PubMed  Google Scholar 

  32. 32.

    Gupta, S. et al. New-onset diabetes and pancreatic cancer. Clin. Gastroenterol. Hepatol. 4, 1366–1372 (2006).

    PubMed  Google Scholar 

  33. 33.

    Munigala, S., Singh, A., Gelrud, A. & Agarwal, B. Predictors for pancreatic cancer diagnosis following new-onset diabetes mellitus. Clin. Transl. Gastroenterol. 6, e118 (2015).

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Maitra, A. et al. A prospective study to establish a new-onset diabetes cohort: from the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas 47, 1244–1248 (2018).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387, 1513–1530 (2016).

    Google Scholar 

  36. 36.

    Stolzenberg-Solomon, R. Z. et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 294, 2872–2878 (2005).

    CAS  PubMed  Google Scholar 

  37. 37.

    Pang, Y. et al. Diabetes, plasma glucose and incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies. Int. J. Cancer 140, 1781–1788 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Grote, V. A. et al. Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Diabetologia 54, 3037–3046 (2011).

    CAS  PubMed  Google Scholar 

  39. 39.

    Michaud, D. S. et al. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA 286, 921–929 (2001).

    CAS  PubMed  Google Scholar 

  40. 40.

    Arslan, A. A. et al. Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch. Intern. Med. 170, 791–802 (2010).

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    World Health Organization. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (2020).

  42. 42.

    Stolzenberg-Solomon, R. Z., Schairer, C., Moore, S., Hollenbeck, A. & Silverman, D. T. Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort. Am. J. Clin. Nutr. 98, 1057–1065 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Nogueira, L., Stolzenberg-Solomon, R., Gamborg, M., Sorensen, T. I. A. & Baker, J. L. Childhood body mass index and risk of adult pancreatic cancer. Curr. Dev. Nutr. 1, e001362 (2017).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Yuan, C. et al. Diabetes, weight change, and pancreatic cancer risk. JAMA Oncol. 6, e202948 (2020).

    PubMed  Google Scholar 

  45. 45.

    Lucenteforte, E. et al. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann. Oncol. 23, 374–382 (2012).

    CAS  PubMed  Google Scholar 

  46. 46.

    Genkinger, J. M. et al. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol. Biomarkers Prev. 18, 765–776 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Jiao, L. et al. Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study. Am. J. Epidemiol. 169, 1043–1051 (2009).

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Gapstur, S. M. et al. Association of alcohol intake with pancreatic cancer mortality in never smokers. Arch. Intern. Med. 171, 444–451 (2011).

    PubMed  Google Scholar 

  49. 49.

    Naudin, S. et al. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study. Int. J. Cancer 143, 801–812 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Yadav, D. & Lowenfels, A. B. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 144, 1252–1261 (2013).

    PubMed  Google Scholar 

  51. 51.

    Duell, E. J. et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann. Oncol. 23, 2964–2970 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Kirkegard, J., Cronin-Fenton, D., Heide-Jorgensen, U. & Mortensen, F. V. Acute pancreatitis and pancreatic cancer risk: a nationwide matched-cohort study in Denmark. Gastroenterology 154, 1729–1736 (2018).

    PubMed  Google Scholar 

  53. 53.

    Gandini, S., Lowenfels, A. B., Jaffee, E. M., Armstrong, T. D. & Maisonneuve, P. Allergies and the risk of pancreatic cancer: a meta-analysis with review of epidemiology and biological mechanisms. Cancer Epidemiol. Biomarkers Prev. 14, 1908–1916 (2005).

    PubMed  Google Scholar 

  54. 54.

    Olson, S. H. et al. Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. Am. J. Epidemiol. 178, 691–700 (2013).

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Cotterchio, M., Lowcock, E., Hudson, T. J., Greenwood, C. & Gallinger, S. Association between allergies and risk of pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 23, 469–480 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Gomez-Rubio, P. et al. Reduced risk of pancreatic cancer associated with asthma and nasal allergies. Gut 66, 314–322 (2017).

    PubMed  Google Scholar 

  57. 57.

    Riquelme, E. et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178, 795–806.e12 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Maisonneuve, P., Amar, S. & Lowenfels, A. B. Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis. Ann. Oncol. 28, 985–995 (2017).

    CAS  PubMed  Google Scholar 

  59. 59.

    Fan, X. et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 67, 120–127 (2018).

    CAS  PubMed  Google Scholar 

  60. 60.

    Michaud, D. S. et al. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut 62, 1764–1770 (2013).

    PubMed  Google Scholar 

  61. 61.

    Schulte, A. et al. Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. Cancer Causes Control. 26, 1027–1035 (2015).

    PubMed  Google Scholar 

  62. 62.

    Andreotti, G. & Silverman, D. T. Occupational risk factors and pancreatic cancer: a review of recent findings. Mol. Carcinog. 51, 98–108 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Barone, E., Corrado, A., Gemignani, F. & Landi, S. Environmental risk factors for pancreatic cancer: an update. Arch. Toxicol. 90, 2617–2642 (2016).

    CAS  PubMed  Google Scholar 

  64. 64.

    Gasull, M. et al. Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. Env. Res. 169, 417–433 (2019).

    CAS  Google Scholar 

  65. 65.

    Antwi, S. O. et al. Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer. Cancer Causes Control. 26, 1583–1591 (2015).

    PubMed  PubMed Central  Google Scholar 

  66. 66.

    Camargo, J. et al. Toenail concentrations of trace elements and occupational history in pancreatic cancer. Env. Int. 127, 216–225 (2019).

    CAS  Google Scholar 

  67. 67.

    Bosch de Basea, M. et al. Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer. Occup. Env. Med. 68, 332–338 (2011).

    CAS  Google Scholar 

  68. 68.

    Amaral, A. F. et al. Pancreatic cancer risk and levels of trace elements. Gut 61, 1583–1588 (2012).

    CAS  PubMed  Google Scholar 

  69. 69.

    Falk, R. T., Pickle, L. W., Fontham, E. T., Correa, P. & Fraumeni, J. F. Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. Am. J. Epidemiol. 128, 324–336 (1988).

    CAS  PubMed  Google Scholar 

  70. 70.

    Friedman, G. D. & Van Den Eeden, S. K. Risk factors for pancreatic cancer: an exploratory study. Int. J. Epidemiol. 22, 30–37 (1993).

    CAS  PubMed  Google Scholar 

  71. 71.

    Fernandez, E., La Vecchia, C., d’Avanzo, B., Negri, E. & Franceschi, S. Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol.Biomarkers Prev. 3, 209–212 (1994).

    CAS  PubMed  Google Scholar 

  72. 72.

    Price, T. F., Payne, R. L. & Oberleitner, M. G. Familial pancreatic cancer in south Louisiana. Cancer Nurs. 19, 275–282 (1996).

    CAS  PubMed  Google Scholar 

  73. 73.

    Ghadirian, P. et al. Reported family aggregation of pancreatic cancer within a population-based case-control study in the francophone community in Montreal, Canada. Int. J. Pancreatol. 10, 183–196 (1991).

    CAS  PubMed  Google Scholar 

  74. 74.

    Coughlin, S. S., Calle, E. E., Patel, A. V. & Thun, M. J. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 11, 915–923 (2000).

    CAS  PubMed  Google Scholar 

  75. 75.

    Schenk, M. et al. Familial risk of pancreatic cancer. J. Natl Cancer Inst. 93, 640–644 (2001).

    CAS  PubMed  Google Scholar 

  76. 76.

    Silverman, D. T. Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog. Carcinog. Mutagen. 21, 7–25 (2001).

    CAS  PubMed  Google Scholar 

  77. 77.

    Jacobs, E. J. et al. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Int. J. Cancer 127, 1421–1428 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Brune, K. A. et al. Importance of age of onset in pancreatic cancer kindreds. J. Natl Cancer Inst. 102, 119–126 (2010).

    PubMed  PubMed Central  Google Scholar 

  79. 79.

    Norris, A. L. et al. Familial and sporadic pancreatic cancer share the same molecular pathogenesis. Fam. Cancer 14, 95–103 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Petersen, G. M. et al. Pancreatic Cancer Genetic Epidemiology Consortium. Cancer Epidemiol. Biomarkers Prev. 15, 704–710 (2006).

    PubMed  Google Scholar 

  81. 81.

    Silverman, D. T. et al. Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br. J. Cancer 80, 1830–1837 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Wang, L. et al. Elevated cancer mortality in the relatives of patients with pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 18, 2829–2834 (2009).

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    McWilliams, R. R. et al. Association of family history of specific cancers with a younger age of onset of pancreatic adenocarcinoma. Clin. Gastroenterol. Hepatol. 4, 1143–1147 (2006).

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Singhi, A. D. et al. A histomorphologic comparison of familial and sporadic pancreatic cancers. Pancreatology 15, 387–391 (2015).

    PubMed  Google Scholar 

  85. 85.

    Shi, C. et al. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin. Cancer Res. 15, 7737–7743 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Chen, F. et al. Analysis of heritability and genetic architecture of pancreatic cancer: a PanC4 study. Cancer Epidemiol. Biomarkers Prev. 28, 1238–1245 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Lichtenstein, P. et al. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).

    CAS  PubMed  Google Scholar 

  88. 88.

    Jones, S. et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324, 217 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Roberts, N. J. et al. ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov. 2, 41–46 (2012).

    CAS  PubMed  Google Scholar 

  90. 90.

    Roberts, N. J. et al. Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov. 6, 166–175 (2016).

    CAS  PubMed  Google Scholar 

  91. 91.

    Amundadottir, L. et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat. Genet. 41, 986–990 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Petersen, G. M. et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet. 42, 224–228 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Wolpin, B. M. et al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat. Genet. 46, 994–1000 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Childs, E. J. et al. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat. Genet. 47, 911–916 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Klein, A. P. et al. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat. Commun. 9, 556 (2018).

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    Brentnall, T. A., Bronner, M. P., Byrd, D. R., Haggitt, R. C. & Kimmey, M. B. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann. Intern. Med. 131, 247–255 (1999).

    CAS  PubMed  Google Scholar 

  97. 97.

    Canto, M. I. et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin. Gastroenterol. Hepatol. 4, 766–781 (2006).

    PubMed  Google Scholar 

  98. 98.

    Canto, M. I. et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 62, 339–347 (2013).

    PubMed  Google Scholar 

  99. 99.

    Canto, M. I. et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 142, 796–804 (2012).

    PubMed  Google Scholar 

  100. 100.

    Vitone, L. J., Greenhalf, W., McFaul, C. D., Ghaneh, P. & Neoptolemos, J. P. The inherited genetics of pancreatic cancer and prospects for secondary screening. Best. Pract. Res. Clin. Gastroenterol. 20, 253–283 (2006).

    CAS  PubMed  Google Scholar 

  101. 101.

    Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    McCabe, N. et al. BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-ribose) polymerase: an issue of potency. Cancer Biol. Ther. 4, 934–936 (2005).

    CAS  PubMed  Google Scholar 

  103. 103.

    van der Heijden, M. S. et al. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin. Cancer Res. 11, 7508–7515 (2005).

    PubMed  Google Scholar 

  104. 104.

    Villarroel, M. C. et al. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol. Cancer Ther. 10, 3–8 (2011).

    CAS  PubMed  Google Scholar 

  105. 105.

    Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409–413 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Fogelman, D. et al. Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. Cancer Chemother. Pharmacol. 76, 489–498 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Zhen, D. B. et al. BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. Genet. Med. 17, 569–577 (2015).

    CAS  PubMed  Google Scholar 

  108. 108.

    Goggins, M. et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 56, 5360–5364 (1996).

    CAS  PubMed  Google Scholar 

  109. 109.

    Hu, C. et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA 319, 2401–2409 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Yurgelun, M. B. et al. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genet. Med. 21, 213–223 (2019).

    CAS  PubMed  Google Scholar 

  111. 111.

    Shindo, K. et al. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J. Clin. Oncol. 35, 3382–3390 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Murphy, K. M. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res. 62, 3789–3793 (2002).

    CAS  PubMed  Google Scholar 

  113. 113.

    Hahn, S. A. et al. BRCA2 germline mutations in familial pancreatic carcinoma. J. Natl Cancer Inst. 95, 214–221 (2003).

    CAS  PubMed  Google Scholar 

  114. 114.

    Couch, F. J. et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 16, 342–346 (2007).

    CAS  PubMed  Google Scholar 

  115. 115.

    Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J. Natl Cancer Inst. 91, 1310–1316 (1999).

    Google Scholar 

  116. 116.

    Mocci, E. et al. Risk of pancreatic cancer in breast cancer families from the Breast Cancer Family Registry. Cancer Epidemiol. Biomarkers Prev. 22, 803–811 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Thompson, D. & Easton, D. F. Cancer incidence in BRCA1 mutation carriers. J. Natl Cancer Inst. 94, 1358–1365 (2002).

    CAS  PubMed  Google Scholar 

  118. 118.

    Tischkowitz, M. D. et al. Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology 137, 1183–1186 (2009).

    PubMed  Google Scholar 

  119. 119.

    Slater, E. P. et al. PALB2 mutations in European familial pancreatic cancer families. Clin. Genet 78, 490–494 (2010).

    CAS  PubMed  Google Scholar 

  120. 120.

    Grant, R. C. et al. Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology 148, 556–564 (2015).

    CAS  PubMed  Google Scholar 

  121. 121.

    Goldstein, A. M., Struewing, J. P., Fraser, M. C., Smith, M. W. & Tucker, M. A. Prospective risk of cancer in CDKN2A germline mutation carriers. J. Med. Genet. 41, 421–424 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Rutter, J. L. et al. Heterogeneity of risk for melanoma and pancreatic and digestive malignancies: a melanoma case-control study. Cancer 101, 2809–2816 (2004).

    PubMed  Google Scholar 

  123. 123.

    Vasen, H. F. et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int. J. Cancer 87, 809–811 (2000).

    CAS  PubMed  Google Scholar 

  124. 124.

    Vasen, H. et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European Expert Centers. J. Clin. Oncol. 34, 2010–2019 (2016).

    CAS  PubMed  Google Scholar 

  125. 125.

    Kastrinos, F. et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA 302, 1790–1795 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126.

    van Lier, M. G. et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am. J. Gastroenterol. 105, 1258–1264 (2009).

    Google Scholar 

  127. 127.

    Giardiello, F. M. et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119, 1447–1453 (2000).

    CAS  PubMed  Google Scholar 

  128. 128.

    Giardiello, F. M. et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N. Engl. J. Med. 316, 1511–1514 (1987).

    CAS  PubMed  Google Scholar 

  129. 129.

    Lowenfels, A. B. et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J. Natl Cancer Inst. 89, 442–446 (1997).

    CAS  PubMed  Google Scholar 

  130. 130.

    Lowenfels, A. B., Maisonneuve, P., Whitcomb, D. C., Lerch, M. M. & DiMagno, E. P. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 286, 169–170 (2001).

    CAS  PubMed  Google Scholar 

  131. 131.

    Vitone, L. J., Greenhalf, W., Howes, N. R., Raraty, M. G. & Neoptolemos, J. P. Trypsinogen mutations in pancreatic disorders. Endocrinol. Metab. Clin. North. Am. 35, 271–287 (2006).

    CAS  PubMed  Google Scholar 

  132. 132.

    Whitcomb, D. C. et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat.Genet. 14, 141–145 (1996).

    CAS  PubMed  Google Scholar 

  133. 133.

    Whitcomb, D. C. et al. A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 110, 1975–1980 (1996).

    CAS  PubMed  Google Scholar 

  134. 134.

    Schubert, S. et al. CFTR, SPINK1, PRSS1, and CTRC mutations are not associated with pancreatic cancer in German patients. Pancreas 43, 1078–1082 (2014).

    CAS  PubMed  Google Scholar 

  135. 135.

    Matsubayashi, H. et al. Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial pancreatic cancer. Cancer Biol. Ther. 2, 652–655 (2003).

    CAS  PubMed  Google Scholar 

  136. 136.

    Tamura, K. et al. Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer. Proc. Natl Acad. Sci. USA 115, 4767–4772 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Zhong, J. et al. A transcriptome-wide association study identifies novel candidate susceptibility genes for pancreatic cancer. J. Natl Cancer Inst. 112, 1003–1012 (2020).

    PubMed  PubMed Central  Google Scholar 

  138. 138.

    Zhang, M. et al. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. Oncotarget 7, 66328–66343 (2016).

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Wu, C. et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat. Genet. 44, 62–66 (2011).

    PubMed  Google Scholar 

  140. 140.

    Low, S. K. et al. Genome-wide association study of pancreatic cancer in Japanese population. PLoS ONE 5, e11824 (2010).

    PubMed  PubMed Central  Google Scholar 

  141. 141.

    Lin, Y. et al. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. Nat. Commun. 11, 3175 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142.

    Childs, E. J. et al. Association of common susceptibility variants of pancreatic cancer in higher-risk patients: a PACGENE Study. Cancer Epidemiol. Biomarkers Prev. 25, 1185–1191 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143.

    Walsh, N. et al. Agnostic pathway/gene set analysis of genome-wide association data identifies associations for pancreatic cancer. J. Natl Cancer Inst. 111, 557–567 (2019).

    PubMed  Google Scholar 

  144. 144.

    US Preventive Services Task Force. Screening for pancreatic cancer: recommendation statement. Am. Fam. Physician 100, 770 (2019).

    Google Scholar 

  145. 145.

    Goggins, M. et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 69, 7–17 (2020).

    CAS  PubMed  Google Scholar 

  146. 146.

    Canto, M. I. et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology 155, 740–751.e2 (2018).

    PubMed  Google Scholar 

  147. 147.

    Overbeek, K. A., Cahen, D. L., Canto, M. I. & Bruno, M. J. Surveillance for neoplasia in the pancreas. Best Pract. Res. Clin. Gastroenterol. 30, 971–986 (2016).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Konings, I. et al. Surveillance for pancreatic cancer in high-risk individuals. BJS Open. 3, 656–665 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Cohen, J. D. et al. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc. Natl Acad. Sci. USA 114, 10202–10207 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Cohen, J. D. et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359, 926–930 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Bartoli, M. et al. CT and MRI of pancreatic tumors: an update in the era of radiomics. Jpn. J. Radiol. 38, 1111–1124 (2020).

    PubMed  Google Scholar 

  152. 152.

    Chu, L. C. et al. Utility of CT radiomics features in differentiation of pancreatic ductal adenocarcinoma from normal pancreatic tissue. AJR Am. J. Roentgenol. 213, 349–357 (2019).

    PubMed  Google Scholar 

Download references

Acknowledgements

The work of the author is supported by NCI RO1CA154823, U01CA247283, NCI P50 CA62924 and P30CA006973, and the Sol Goldman Pancreatic Cancer Research Center.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Alison P. Klein.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks the anonymous reviewers for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

National Cancer Institute. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program: https://seer.cancer.gov/explorer/

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Klein, A.P. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 18, 493–502 (2021). https://doi.org/10.1038/s41575-021-00457-x

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing