Skip to main content

Advertisement

SpringerLink
Log in

Assessment of “Gene–Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer

  • SSAT Poster Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. This study characterizes one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures, and survival status.

Background

Reported risk factors for PC include advancing age, a family history of PC, high-risk inherited syndromes, cigarette, cigar, and pipe smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus.

Patients and Methods

This retrospective cross-sectional, case-only analysis includes cases of FPC (n = 569) and SPC (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005.

Results

FPC smokers with environmental tobacco smoke (ETS) exposure were diagnosed at a significantly younger mean age (63.7 years) as compared to FPC non-smokers without ETS exposure (66.6 years; p = 0.05). Non-smoker ETS-exposed cases were diagnosed with PC at a significantly younger mean age (64.0 years) compared to non-smoker non-ETS-exposed cases (66.5 years) (p < 0.0004). The mean age at diagnosis for Ashkenazi Jewish SPC subjects was significantly younger (by 2.1 years) than Ashkenazi Jewish FPC cases (p = 0.05). In addition, Ashkenazi Jewish FPC subjects who smoked were diagnosed 5.9 years earlier than Ashkenazi Jewish FPC non-smokers (p = 0.05). The median length of survival for unresected FPC cases was significantly shorter (168 days) as compared to unresected SPC cases (200 days) (p = 0.04). Survival was improved in resected cases, 713 days for FPC cases and 727 days for SPC cases, but was not significantly different between the groups (p = 0.4). Mild to moderate multiplicative interaction was found between a family history of PC and exposure to asbestos, environmental radon, and environmental tobacco smoke (ETS), as evidenced by odds ratios >1.0.

Conclusions

These are the first data to show that occupational and environmental exposures may act synergistically with inherited or acquired genetic polymorphisms, resulting in earlier occurrence of PC. Exposure to cigarette smoking and ETS exposure in non-smokers when younger than 21 years of age are associated with a younger mean age of diagnosis in FPC and SPC cases and Ashkenazi Jewish smokers, when compared to non-exposed cases. Risk prediction models which take into account environmental exposures as well as family history may more accurately predict the risk of PC. High-risk individuals will likely benefit from early identification of pre-malignant lesions and molecular profiling, as methods of early detection, prevention, and personalized therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. American Cancer Society. Cancer facts and figures. Atlanta: American Cancer Society, 2008.

    Google Scholar 

  2. Hruban R, Petersen G, Ha P, Kern S. Genetics of pancreatic cancer. Surg Oncol Clin N Am 1998;7(1):1–23.

    CAS  PubMed  Google Scholar 

  3. Arnold M, Goggins M. BRCA2 and predisposition to pancreatic and other Cancers. Expert Reviews in Molecular Medicine:http://www-ermm.cbcu.cam.ac.uk Accession information (01)00309-Xh.htm(shortcode:txt001mgb); 14 May 2001.

  4. Gold E, Goldin S. Epidemiology of and risk factors for pancreatic cancer. Surg Oncol Clin N Am 1998;7(1):67–91.

    CAS  PubMed  Google Scholar 

  5. Lowenfels A, Maisonneuve E. Epidemiologic and etiologic factors of pancreatic cancer. Hematol Oncol Clin North Am 2002;16(1):1–16. doi:10.1016/S0889-8588(01)00003-X.

    Article  PubMed  Google Scholar 

  6. Lowenfels A, Maisonneuve E. Epidemiology and prevention of pancreatic cancer. Jpn J Clin Oncol 2004;34(5):238–244. doi:10.1093/jjco/hyh045.

    Article  PubMed  Google Scholar 

  7. Iodice S, Gandini S, Maisonneuve P, Lowenfels A. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg 2008;393:535–545. doi:10.1007/s00423-007-0266-2.

    Article  PubMed  Google Scholar 

  8. Yeo T, Hruban R, Leach S, Wilentz R, Sohn T, Kern S, Iacobuzio-Donahue C, Maitra A, Goggins M, Canto M, Abrams R, Laheru D, Jaffee E, Hidalgo M, Yeo CJ. Pancreatic cancer. Curr Probl Cancer 2002;26(4):165–276. doi:10.1067/mcn.2002.129579.

    Article  Google Scholar 

  9. Silverman D, Dunn J, Hoover R, Schiffman M, Lillemoe K, Schoenberg J, Brown L, Greenberg R, Hayes R, Swanson M, Wacholder S, Schwartz A, Liff J, Pottern L. Cigarette smoking and pancreas cancer: a case–control study based on direct interviews. J Natl Cancer Inst 1994;86(20):1510–1516. doi:10.1093/jnci/86.20.1510.

    Article  CAS  PubMed  Google Scholar 

  10. Howe G, Jain M, Burch J, Miller A. Cigarette smoking and cancer of the pancreas: evidence from a population-based case–control study in Toronto, Canada. Int J Cancer 1991;47:323–328. doi:10.1002/ijc.2910470302.

    Article  CAS  PubMed  Google Scholar 

  11. Ishii K, Nakamura K, Okzzaki H et al. (in Japanese). Nippon Rinsho, 26, 1839–1842. (quoted in Ahlgren, Ahlgren, J. (1996). Epidemiology and risk factors in pancreatic cancer. Semin Oncol 1968;23(2):241–250.

    Google Scholar 

  12. Husgafvel-Pursiainen K. Genotoxicity of environmental tobacco smoke: a review. Mutat Res 2004;567:427–445. doi:10.1016/j.mrrev.2004.06.004.

    Article  CAS  PubMed  Google Scholar 

  13. Kasim K, Levallois P, Abdous B, Auger P, Johnson K, The Canadian Cancer Registries Epidemiology Research Group. Environmental tobacco smoke and risk of adult leukemia. Epidemiology 2005;16(5):672–680. doi:10.1097/01.ede.0000173039.79207.80.

    Article  PubMed  Google Scholar 

  14. National Cancer Institute. (March 7, 2000). Cancer Facts. Accessed at: http://cis.nci.nih.gov/fact/3_65.htm. National Center for Health Statistics. Health, United States, 2000 with Urban and Rural Chartbook. Hyattsville, MD: Public Health Service; 2001.

  15. International Agency for Research on Cancer (IARC). Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risk Chem Hum 2004;83:1–1452.

    Google Scholar 

  16. Villeneuve P, Johnson K, Hanley A. 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):32–37.

    PubMed  Google Scholar 

  17. Falk R, Pickle L, Fontham E, Correa P, Morse A, Chen V, Fraumeni J. Occupation and pancreatic cancer risk in Louisiana. Am J Ind Med 1990;18:565–576.

    Article  CAS  PubMed  Google Scholar 

  18. Rotimi C, Austin H, Delzell E, Day C, Macaluso M, Honda Y. Retrospective follow-up study of foundry and engine plant workers. Am J Ind Med 1993;24:485–498.

    Article  CAS  PubMed  Google Scholar 

  19. Ojajarvi I, Partanen T, Ahlbom A, Biffetta P, Hakulinen T, Jourenkova N, Kauppinen T, Kogevinas M, Porta M, Vainio H, Weiderpass E, Wesseling C. Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med 2000;57(5):316–324.

    Article  CAS  PubMed  Google Scholar 

  20. Bu-Tian J, Silverman D, Stewart P, Blair A, Swanson G, Bartis D, Greenberg R, Hayes R, Brown L, Lillemoe K, Schoenberg J, Pottern L, Schwartz, Hoover R. Occupational exposures to pesticides and pancreatic cancer. Am J Ind Med 2001;39:92–99.

    Article  Google Scholar 

  21. Krush A, Giardiello F. Development of a genetics registry: Hereditary intestinal polyposis and hereditary colon cancer registry at The Johns Hopkins Hospital, 1973–1988. In Herrera L, ed. Familial adenomatous polyposis. New York: Liss, 1990, pp 43–59.

    Google Scholar 

  22. Gauderman J. Quanto®. Version 1.0. Accessed: http://hydra.usc.edu/gxe Stata® Version 7.0 (2002). Stata Corporation, College Station, Texas. http://www.stata.com, 2002.

  23. U.S. Department of Labor, Bureau of Labor Statistics. 2000 Standard Occupational Classification User Guide (on-line). Accessed 3/4/06. at: http://www.bls.gov/soc/socguide.htm.

  24. Hecht S. Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol 2002;1:461–469.

    Article  Google Scholar 

  25. Diethelm P, Rielle J, McKee M. The whole truth and nothing but the truth? The research that Philip Morris did not want you to see. Lancet 2005;366:86–92.

    Article  PubMed  Google Scholar 

  26. Mohtashamipur E, Mohtashamipur A, Germann P, Ernst H, Norpoth K, Mohr U. Comparative carcinogenicity of cigarette mainstream and sidestream smoke condensates on the mouse skin. J Cancer Res Clin Oncol 1990;116:604–608.

    Article  CAS  PubMed  Google Scholar 

  27. McWilliams R, Bamlet W, Cunningham J, Goode E, de Andrade M, Boardman L, Petersen G. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res 2008;68:4928–4935.

    Article  CAS  PubMed  Google Scholar 

  28. Lee PN. Environmental tobacco smoke and cancer of sites other than the lung in adult non-smokers. Food Chem Toxicol 2002;40(6):747–766.

    Article  PubMed  Google Scholar 

  29. Brownson R, Figgs L, Caisley L. Epidemiology of environmental smoke and lung cancer in nonsmoking women. Oncogene 2002;21:7341–7348. 30.

    Article  CAS  PubMed  Google Scholar 

  30. Wang W, Chen S, Brune K, Hruban R, Parmigiani G, Klein A. PancPRO: risk assessment for individuals with a family history of pancreatic cancer. J Clin Oncol 2007;25:1417–1422.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Thomas Jefferson University School of Nursing, Edison Building, 130 S. 9th Street, Suite 1252, Philadelphia, PA, 19107, USA

    Theresa P. Yeo

  2. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD, USA

    Ralph H. Hruban & Kieran Brune

  3. Department of Surgery, and the Jefferson Pancreas, Biliary and Related Cancers Center, Thomas Jefferson University, Philadelphia, PA, USA

    Jonathan Brody & Charles J. Yeo

  4. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Theresa P. Yeo & Sheila Fitzgerald

Authors
  1. Theresa P. Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralph H. Hruban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan Brody
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kieran Brune
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sheila Fitzgerald
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Charles J. Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theresa P. Yeo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yeo, T.P., Hruban, R.H., Brody, J. et al. Assessment of “Gene–Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer. J Gastrointest Surg 13, 1487–1494 (2009). https://doi.org/10.1007/s11605-009-0923-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-009-0923-6

Keywords

Search

Navigation