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Familial pancreatic cancer risk: a population-based study in Utah

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Introduction

Pancreas adenocarcinoma (PC) has an undefined hereditary component. We quantified the familial risk of PC among relatives of patients diagnosed with PC and stratified it based on anatomic location of PC and age and sex of the proband.

Methods

This is a retrospective, population-based, case–control study of PC diagnosed in Utah between 1980 and 2011. The Utah population database and cancer registry were used to identify index patients with PC. The risk of PC in first-degree relatives (FDRs), second-degree relatives (SDRs), and first cousins (FCs) of probands was compared with randomly selected sex- and age-matched population controls.

Results

A total of 4,095 patients and 40,933 controls were identified. The relative risk (RR) of PC was 1.76 (95% CI 1.35–2.29) in FDRs, 1.42 (95% CI 1.18–1.7) in SDRs and 1.08 (95% CI 0.95–1.23) in FCs of probands compared to relatives of PC-free controls. The RR were elevated in FDRs (1.96, 95% CI 1.45–2.65), SDRs (1.54, 95% CI 1.19–1.98) and FCs (1.18, 95% CI 1.0–1.64) of female probands. Among probands diagnosed as < 65 years, RR was 2.12 (95% CI 1.37–3.28) in FDRs, 1.94 (95% CI 1.44–2.62) in SDRs, and 1.28 (95% CI 1.0–1.64) in FCs. Overall, the RR for PC was elevated in FDRs regardless of the anatomic location of PC.

Discussion

There is an increased risk of PC in FDR and more distant relatives of patients with PC. Relatives of female patients with PC and patients diagnosed at age < 65 years are at a significantly increased risk of PC.

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Abbreviations

PC:

Pancreas adenocarcinoma

UCR:

Utah cancer registry

UPDB:

Utah population database

FDR:

First-degree relative (parent, child, sibling)

SDR:

Second-degree relative (aunt/uncle, niece/nephew, grandparent/grandchild)

FC:

First cousin

RR:

Relative risk

References

  1. Chiaravalli M, Reni M, O’Reilly EM. Pancreatic ductal adenocarcinoma: State-of-the-art 2017 and new therapeutic strategies. Cancer Treat Rev. 2017;60:32–433.

    Article  Google Scholar 

  2. Kohli DR, Kapoor A, BouHaidar D, et al. Requirement of a single high-risk feature as an indication for EUS for the diagnosis of asymptomatic pancreatic cysts. Pancreatology. 2016;16:1015–9.

    Article  Google Scholar 

  3. Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62:339–47.

    Article  Google Scholar 

  4. Shirts BH, Burt RW, Mulvihill SJ, et al. A population-based description of familial clustering of pancreatic cancer. Clin Gastroenterol Hepatol. 2010;8:812–6.

    Article  Google Scholar 

  5. Samadder NJ, Smith KR, Wong J, et al. Familial risk of biliary tract cancers: a population-based study in Utah. Dig Dis Sci. 2016;61:3627–32.

    Article  Google Scholar 

  6. Samadder NJ, Curtin K, Wong J et al (2014) Epidemiology and familial risk of synchronous and metachronous colorectal cancer: a population-based study in Utah. Clin Gastroenterol Hepatol 12:2078–2084.e1–2

    Article  Google Scholar 

  7. Jorde LB. Inbreeding in the Utah Mormons: an evaluation of estimates based on pedigrees, isonymy, and migration matrices. Ann Hum Genet. 1989;53(Pt 4):339–55.

    Article  CAS  Google Scholar 

  8. Samadder NJ, Smith KR, Hanson H, et al. Familial risk in patients with carcinoma of unknown primary. JAMA Oncol. 2016;2:340–6.

    Article  Google Scholar 

  9. Curtin K, Smith KR, Fraser A, et al. Familial risk of childhood cancer and tumors in the Li-Fraumeni spectrum in the Utah Population Database: implications for genetic evaluation in pediatric practice. Int J Cancer. 2013;133:2444–533.

    Article  CAS  Google Scholar 

  10. Samadder NJ, Curtin K, Tuohy TMF, et al. Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah. Gastroenterology. 2014;147:814–21.

    Article  Google Scholar 

  11. Schenk M, Schwartz AG, O’Neal E, et al. Familial risk of pancreatic cancer. J Natl Cancer Inst. 2001;93:640–4.

    Article  CAS  Google Scholar 

  12. Tersmette AC, Petersen GM, Offerhaus GJ, et al. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res. 2001;7:738–44.

    CAS  PubMed  Google Scholar 

  13. Becker AE, Hernandez YG, Frucht H, et al. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J Gastroenterol. 2014;20:11182–98.

    Article  Google Scholar 

  14. Permuth-Wey J, Egan KM. Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis. Fam Cancer. 2009;8:109–17.

    Article  Google Scholar 

  15. Austin MA, Kuo E, Van Den Eeden SK, et al. Family history of diabetes and pancreatic cancer as risk factors for pancreatic cancer: the PACIFIC study. Cancer Epidemiol Biomark Prev. 2013;22:1913–7.

    Article  Google Scholar 

  16. Jacobs EJ, Chanock SJ, Fuchs CS, et al. Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Int J Cancer. 2010;127:1421–8.

    Article  CAS  Google Scholar 

  17. Hassan MM, Bondy ML, Wolff RA, et al. Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol. 2007;102:2696–707.

    Article  Google Scholar 

  18. Hruban RH, Petersen GM, Goggins M, et al. Familial pancreatic cancer. Ann Oncol. 1999;10(Suppl 4):69–73.

    Article  Google Scholar 

  19. Love RR, Evans AM, Josten DM. The accuracy of patient reports of a family history of cancer. J Chronic Dis. 1985;38:289–93.

    Article  CAS  Google Scholar 

  20. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol. 2005;7:189–97.

    Article  Google Scholar 

  21. Zator Z, Whitcomb DC. Insights into the genetic risk factors for the development of pancreatic disease. Ther Adv Gastroenterol. 2017;10:323–36.

    Article  CAS  Google Scholar 

  22. Brune KA, Lau B, Palmisano E, et al. Importance of age of onset in pancreatic cancer kindreds. J Natl Cancer Inst. 2010;102:119–26.

    Article  Google Scholar 

  23. Matsubayashi H, Maeda A, Kanemoto H, et al. Risk factors of familial pancreatic cancer in Japan: current smoking and recent onset of diabetes. Pancreas. 2011;40:974–8.

    Article  Google Scholar 

  24. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64:2634–8.

    Article  CAS  Google Scholar 

  25. Molina-Montes E, Gomez-Rubio P, Márquez M, et al. Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives. Int J Epidemiol. 2018;47:473–83.

    Article  CAS  Google Scholar 

  26. Lu C, Xu C-F, Wan X-Y, et al. Screening for pancreatic cancer in familial high-risk individuals: a systematic review. World J Gastroenterol. 2015;21:8678–86.

    Article  Google Scholar 

  27. Paiella S, Salvia R, De Pastena M, et al. Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: a systematic review and proportion meta-analysis of screening results. Pancreatology. 2018;18:420–8.

    Article  Google Scholar 

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Funding

The study was funded by the National Cancer Institute, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy and the Huntsman Cancer Foundation. The funding sources did not play a role in the design, conduct or reporting of the study or in the decision to submit the manuscript for publication. Support for this project was provided by NCI grants P01-CA073992 (RWB), R01-CA040641 (RWB), an Endoscopic Research Award from the American Society for Gastrointestinal Endoscopy (NJS) and a Junior Faculty Career Development Award from the American College of Gastroenterology (NJS). Partial support for the Utah Population Database and this project was provided by the Huntsman Cancer Institute Cancer Center Support Grant P30CA042014 from the National Cancer institute and the Huntsman Cancer Foundation. Support for the Utah Cancer Registry is provided by Contract #HHSN 261201000026C from the National Cancer Institute with additional support from the Utah Department of Health and the University of Utah.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA

    Divyanshoo R. Kohli, Douglas O. Faigel, Rahul Pannala & N. Jewel Samadder

  2. Department of Medicine (Gastroenterology), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Ken Robert Smith, Jathine Wong, Zhe Yu, Kenneth Boucher, Randall W. Burt & Karen Curtin

  3. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Ken Robert Smith, Jathine Wong, Zhe Yu, Kenneth Boucher, Randall W. Burt & Karen Curtin

  4. Department of Medicine (Genetic Epidemiology), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Ken Robert Smith, Jathine Wong, Zhe Yu, Kenneth Boucher, Randall W. Burt & Karen Curtin

  5. Division of Gastroenterology and Hepatology, Kansas City Veterans Affairs Medical Center, Kansas City, MO, USA

    Divyanshoo R. Kohli

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  1. Divyanshoo R. Kohli
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  2. Ken Robert Smith
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  5. Kenneth Boucher
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  8. Randall W. Burt
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  9. Karen Curtin
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  10. N. Jewel Samadder
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Contributions

Drs. Samadder and Curtin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses. Study concept and design: RWB, KC, NJS; acquisition, analysis and interpretation of data: GM, KS, DK, KC, JW, RP, KB, LP, RWB, NJS; drafting of the manuscript: DK, KC, and NJS; critical revision of the manuscript for important intellectual content: DK, GM, KC, KS, HS, DA, DF, RP, RWB; statistical analysis: JW, KC, LP; obtained funding: NJS and RWB.

Corresponding author

Correspondence to N. Jewel Samadder.

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Conflict of interest

NJS is a consultant for Cook Medical, Cancer Prevention Pharmaceuticals and Janssen Research and Development. No other authors have a conflict of interest to disclose.

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Kohli, D.R., Smith, K.R., Wong, J. et al. Familial pancreatic cancer risk: a population-based study in Utah. J Gastroenterol 54, 1106–1112 (2019). https://doi.org/10.1007/s00535-019-01597-3

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  • DOI: https://doi.org/10.1007/s00535-019-01597-3

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