Hereditary Pancreatitis and the Risk of Pancreatic Cancer
Abstract
BACKGROUND: Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. PURPOSE: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. METHODS: To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (< or = 30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. RESULTS: The mean age (+/- standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 +/- 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age +/- SD at diagnosis of pancreatic cancer: 56.9 +/- 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23-105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3-1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. CONCLUSIONS: Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PRSS1, CPA1 and CTRC are associated with significantly increased risk of developing pancreatitis.
“The pancreatitis susceptibility genes, PRSS1, CPA1 and CTRC, are associated with significantly increased risk of developing pancreatitis.”
Cites
Cancer Incidence in Five Continents
Doll, R., Muir, C. S., & Waterhouse, J. A. H. (1970) · Springer eBooks · doi:10.1007/978-3-642-85851-2 · Cited by 8,485 · see citing works
Pancreatitis and the Risk of Pancreatic Cancer
Lowenfels, A. B., Maisonneuve, P., Cavallini, G., Ammann, R., Lankisch, P. G., Andersen, J. R., DiMagno, E. P., Andrén‐Sandberg, Å., & Domellöf, L. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282001 · Cited by 1,753 · see citing works
Self-citationHereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene
Whitcomb, D. C., Gorry, M. C., Preston, R. A., Furey, W. F., Sossenheimer, M. J., Ulrich, C. D., Martin, S. P., Gates, L. K., Amann, S. T., Toskes, P. P., et al. (1996) · Nature Genetics · doi:10.1038/ng1096-141 · Cited by 1,616 · see citing works
Self-citationIncreased cell division as a cause of human cancer.
Preston‐Martin, S., Pike, M. C., Ross, R. K., Jones, P. A., & Henderson, B. E. (1990) · PubMed · Cited by 896 · see citing works
Barlow, D. P. (1995) · Science · doi:10.1126/science.270.5242.1610 · Cited by 438 · see citing works
DNA methylation errors and cancer.
Jones, P. A. (1996) · PubMed · Cited by 399 · see citing works
A gene for hereditary pancreatitis maps to chromosome 7q35
Whitcomb, D., Preston, R., Aston, C. E., et al. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8964426 · Cited by 330 · see citing works
Self-citationPancreatitis is a risk factor for pancreatic cancer
Bansal, P., & Sonnenberg, A. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90291-0 · Cited by 286 · see citing works
The Exocrine Pancreas: Biology, Pathobiology, and Diseases.
(1986) · Annals of Internal Medicine · doi:10.7326/0003-4819-105-2-326_2 · Cited by 243 · see citing works
Pancreatitis and Pancreatic Cancer: a Population-Based Study
Ekbom, A., McLaughlin, J. K., Karlson, B., Nyrén, O., Gridley, G., Adami, H., & Fraumeni, J. F. (1994) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/86.8.625 · Cited by 211 · see citing works
The hereditary pancreatitis gene maps to long arm of chromosome 7
Bodic, L. L. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.4.549 · Cited by 198 · see citing works
Cancer incidence in five continents, vol. VI
Levi, F. (1993) · European Journal of Cancer · doi:10.1016/0959-8049(93)90227-7 · Cited by 197 · see citing works
HEREDITARY PANCREATITIS: THREE NEW KINDREDS AND A CRITICAL REVIEW OF THE LITERATURE
Kattwinkel, J., Lapey, A., di Sant'Agnese, P. A., Edwards, W. A., & Hufty, M. P. (1973) · PEDIATRICS · doi:10.1542/peds.51.1.55 · Cited by 130 · see citing works
Pancreatitis and the Risk of Pancreatic Cancer
Fernández, E., Vecchia, C. L., Porta, M. S., et al. (1995) · Pancreas · doi:10.1097/00006676-199508000-00012 · Cited by 105 · see citing works
Hereditary pancreatitis in England and Wales.
Sibert, J. R. (1978) · Journal of Medical Genetics · doi:10.1136/jmg.15.3.189 · Cited by 97 · see citing works
IMPRINTING THE GENOME: IMPRINTED GENES, IMPRINTING GENES, AND A HYPOTHESIS FOR THEIR INTERACTION
Peterson, K., & Sapienza, C. (1993) · Annual Review of Genetics · doi:10.1146/annurev.ge.27.120193.000255 · Cited by 59 · see citing works
Genomic Imprinting, DNA Methylation, and Cancer
Rainier, S. R., & Feinberg, A. P. (1994) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/86.13.1028 · Cited by 50 · see citing works
The Surgical Spectrum of Hereditary Pancreatitis in Adults
Miller, A. R., Nagorney, D. M., & Sarr, M. G. (1992) · Annals of Surgery · doi:10.1097/00000658-199201000-00006 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors
Rawla, P., Sunkara, T., & Gaduputi, V. (2019) · World Journal of Oncology · doi:10.14740/wjon1166 · Cited by 2,269 · see citing works
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
Canto, M. I., Harinck, F., Hruban, R. H., Offerhaus, G. J., Poley, J.-W., Kamel, I., Nio, Y., Schulick, R. S., Bassi, C., Kluijt, I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-303108 · Cited by 784 · see citing works
Maitra, A., & Hruban, R. H. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154305 · Cited by 707 · see citing works
Kopp, J. L., von Figura, G., Mayes, E., Liu, F.-F., Dubois, C. L., Morris, J. P., Pan, F. C., Akiyama, H., Wright, C. V. E., Jensen, K., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.10.025 · Cited by 697 · see citing works
Goggins, M., Overbeek, K. A., Brand, R., Syngal, S., Del Chiaro, M., Bartsch, D. K., Bassi, C., Carrato, A., Farrell, J., Fishman, E. K., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319352 · Cited by 659 · see citing works
Risk of Pancreatic Cancer in Families With Lynch Syndrome
Kastrinos, F. (2009) · JAMA · doi:10.1001/jama.2009.1529 · Cited by 544 · see citing works
Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study
Canto, M. I., Goggins, M., Hruban, R. H., Petersen, G. M., Giardiello, F. M., Yeo, C., Fishman, E. K., Brune, K., Axilbund, J., Griffin, C., et al. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.02.005 · Cited by 524 · see citing works
BRCA2 germline mutations in familial pancreatic carcinoma
Hahn, S. A., Greenhalf, B., Ellis, I., Sina-Frey, M., Rieder, H., Korte, B., Gerdes, B., Kress, R., Ziegler, A., Raeburn, J. A., et al. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.3.214 · Cited by 480 · see citing works
Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach
Canto, M. I., Goggins, M., Yeo, C. J., Griffin, C., Axilbund, J. E., Brune, K., Ali, S. Z., Jagannath, S., Petersen, G. M., Fishman, E. K., et al. (2004) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(04)00244-7 · Cited by 448 · see citing works
<i>STAT3</i> Plays a Critical Role in <i>KRAS</i> -Induced Pancreatic Tumorigenesis
Corcoran, R. B., Contino, G., Deshpande, V., Tzatsos, A., Conrad, C., Benes, C. H., Levy, D. E., Settleman, J., Engelman, J. A., & Bardeesy, N. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0908 · Cited by 413 · see citing works
Inflammation and the development of pancreatic cancer
Farrow, B., & Evers, B. M. (2002) · Surgical Oncology · doi:10.1016/s0960-7404(02)00015-4 · Cited by 338 · see citing works
Curran, E. A., O'Neill, S. M., Cryan, J. F., Kenny, L. C., Dinan, T. G., Khashan, A. S., & Kearney, P. M. (2015) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12351 · Cited by 250 · see citing works
Gangi, S., Fletcher, J. G., Nathan, M. A., Christensen, J. A., Harmsen, W. S., Crownhart, B. S., & Chari, S. T. (2004) · American Journal of Roentgenology · doi:10.2214/ajr.182.4.1820897 · Cited by 249 · see citing works
NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma
Daley, D., Mani, V. R., Mohan, N., Akkad, N., Pandian, G. S. D. B., Savadkar, S., Lee, K. B., Torres-Hernandez, A., Aykut, B., Diskin, B., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20161707 · Cited by 244 · see citing works
Molecular markers of early pancreatic cancer
Goggins, M. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.19.711 · Cited by 214 · see citing works
Verna, E. C., Hwang, C., Stevens, P. D., Rotterdam, H., Stavropoulos, S. N., Sy, C. D., Prince, M. A., Chung, W. K., Fine, R. L., Chabot, J. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3209 · Cited by 201 · see citing works
CDKN2A Germline Mutations in Familial Pancreatic Cancer
Bartsch, D. K., Sina-Frey, M., Lang, S., Wild, A., Gerdes, B., Barth, P., Kress, R., Grützmann, R., Colombo-Benkmann, M., Ziegler, A., et al. (2002) · Annals of Surgery · doi:10.1097/00000658-200212000-00005 · Cited by 186 · see citing works
Molecular pathogenesis of pancreatic cancer
Hansel, D. E., Kern, S. E., & Hruban, R. H. (2003) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.4.070802.110341 · Cited by 159 · see citing works
Petersen, G. M. (2016) · Seminars in Oncology · doi:10.1053/j.seminoncol.2016.09.002 · Cited by 157 · see citing works
Epithelial and stromal co-evolution and complicity in pancreatic cancer
Hingorani, S. R. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00530-w · Cited by 108 · see citing works
Corral, J. E., Mareth, K. F., Riegert-Johnson, D. L., Das, A., & Wallace, M. B. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.04.065 · Cited by 113 · see citing works
Abe, T., Blackford, A. L., Tamura, K., Ford, M., McCormick, P., Chuidian, M., Almario, J. A., Borges, M., Lennon, A. M., Shin, E. J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.01512 · Cited by 102 · see citing works
Tamura, K., Yu, J., Hata, T., Suenaga, M., Shindo, K., Abe, T., MacGregor-Das, A., Borges, M., Wolfgang, C. L., Weiss, M. J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720588115 · Cited by 95 · see citing works
Genetics of familial and sporadic pancreatic cancer
Wood, L. D., Yurgelun, M. B., & Goggins, M. G. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.039 · Cited by 91 · see citing works
Perusina Lanfranca, M., Zhang, Y., Girgis, A., Kasselman, S., Lazarus, J., Kryczek, I., Delrosario, L., Rhim, A., Koneva, L., Sartor, M., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.010 · Cited by 81 · see citing works
Anderson, M. A., Zolotarevsky, E., Cooper, K. L., Sherman, S., Shats, O., Whitcomb, D. C., Lynch, H. T., Ghiorzo, P., Rubinstein, W. S., Vogel, K. J., et al. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.288 · Cited by 73 · see citing works
Self-citationCost-effectiveness of Pancreatic Cancer Surveillance in High-Risk Individuals: An Economic Analysis
Corral, J. E., Das, A., Bruno, M. J., & Wallace, M. B. (2019) · Pancreas · doi:10.1097/mpa.0000000000001268 · Cited by 66 · see citing works
The role of endoscopic ultrasound in pancreatic cancer screening
Bhutani, M., Koduru, P., Joshi, V., Saxena, P., Suzuki, R., Irisawa, A., & Yamao, K. (2016) · Endoscopic Ultrasound · doi:10.4103/2303-9027.175876 · Cited by 55 · see citing works
Delayed sleeve gastrectomy following liver transplantation: a 5-year experience
Morris, M. C., Jung, A. D., Kim, Y., Lee, T. C., Kaiser, T. E., Thompson, J. R., Bari, K., Shah, S. A., Cohen, R. M., Schauer, D. P., et al. (2019) · Liver Transplantation · doi:10.1002/lt.25637 · Cited by 45 · see citing works
No evidence for germline mutations of the LKB1/STK11 gene in familial pancreatic carcinoma
Grützmann, R., McFaul, C., Bartsch, D. K., Sina-Frey, M., Rieder, H., Koch, R., McCarthy, E., Greenhalf, W., Neoptolemos, J. P., Saeger, H. D., et al. (2004) · Cancer Letters · doi:10.1016/j.canlet.2004.06.012 · Cited by 23 · see citing works
- Authors
- Lowenfels, A. B., Maisonneuve, P., DiMagno, E. P., Elitsur, Y., Gates, L. K., Perrault, J., Whitcomb, D. C., & International Hereditary Pancreatitis Study Group
- Affiliations
- New York Medical College (US)
- European Institute of Oncology (IT)
- Mayo Clinic (US)
- Marshall University (US)
- University of Kentucky (US)
- University of Pittsburgh (US)
- Corresponding author
- Lowenfels, A. B.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-03-19
- Volume
- 89
- Issue
- 6
- Pages
- 442-446
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2050164769
- Cited by
- 988
- References
- 18
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 22 · 2023: 20 · 2022: 29 · 2021: 40 · 2020: 23 · 2019: 29 · 2018: 40 · 2017: 44 · 2016: 43 · 2015: 32 · 2014: 40 · 2013: 28 · 2012: 45
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- hereditary pancreatitis, pancreatic cancer, pancreatic ductal adenocarcinoma, chronic pancreatitis, SPINK1, pancreatic cancer risk, standardized incidence ratio, natural history (disease), pancreatic neoplasms, pancreatic cysts, pancreatic ductal adenoma, pancreatic neuroendocrine tumors, pancreatic neuroendocrine carcinoma, pancreatic cystic neoplasms
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Longitudinal Studies, Male, Pancreatic Neoplasms, Pancreatitis, Risk, Incidence, Odds Ratio, Age of Onset
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
