© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 442-446, Copyright © 1997 by Oxford University Press
AB Lowenfels, P Maisonneuve, EP DiMagno, Y Elitsur, LK Gates Jr, J Perrault and DC Whitcomb
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.
REVIEWS
Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group
Department of Surgery, New York Medical College, Valhalla 10595, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Kastrinos, B. Mukherjee, N. Tayob, F. Wang, J. Sparr, V. M. Raymond, P. Bandipalliam, E. M. Stoffel, S. B. Gruber, and S. Syngal Risk of Pancreatic Cancer in Families With Lynch Syndrome JAMA, October 28, 2009; 302(16): 1790 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Kume, A Masamune, Y Takagi, K Kikuta, T Watanabe, K Satoh, A Satoh, M Hirota, S Hamada, and T Shimosegawa A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders Gut, June 1, 2009; 58(6): 820 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Klein, M. Borges, M. Griffith, K. Brune, S.-M. Hong, N. Omura, R. H. Hruban, and M. Goggins Absence of Deleterious Palladin Mutations in Patients with Familial Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2009; 18(4): 1328 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Wolpin, A. T. Chan, P. Hartge, S. J. Chanock, P. Kraft, D. J. Hunter, E. L. Giovannucci, and C. S. Fuchs ABO Blood Group and the Risk of Pancreatic Cancer J Natl Cancer Inst, March 18, 2009; 101(6): 424 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Larghi, E. C. Verna, P. G. Lecca, and G. Costamagna Screening for Pancreatic Cancer in High-Risk Individuals: A Call for Endoscopic Ultrasound Clin. Cancer Res., March 15, 2009; 15(6): 1907 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Rebours, M-C Boutron-Ruault, M Schnee, C Ferec, C Le Marechal, O Hentic, F Maire, P Hammel, P Ruszniewski, and P Levy The natural history of hereditary pancreatitis: a national series Gut, January 1, 2009; 58(1): 97 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. D. Foulkes Inherited Susceptibility to Common Cancers N. Engl. J. Med., November 13, 2008; 359(20): 2143 - 2153. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lee, J. Dosch, and D. M. Simeone Pancreatic Cancer Stem Cells J. Clin. Oncol., June 10, 2008; 26(17): 2806 - 2812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E Brand, M. M Lerch, W. S Rubinstein, J. P Neoptolemos, D. C Whitcomb, R. H Hruban, T. A Brentnall, H. T Lynch, M. I Canto, and Participants of the Fourth International Symposium Advances in counselling and surveillance of patients at risk for pancreatic cancer Gut, October 1, 2007; 56(10): 1460 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Infante, H. Matsubayashi, N. Sato, J. Tonascia, A. P. Klein, T. A. Riall, C. Yeo, C. Iacobuzio-Donahue, and M. Goggins Peritumoral Fibroblast SPARC Expression and Patient Outcome With Resectable Pancreatic Adenocarcinoma J. Clin. Oncol., January 20, 2007; 25(3): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hirota, M. Ohmuraya, and H. Baba Genetic background of pancreatitis Postgrad. Med. J., December 1, 2006; 82(974): 775 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Dev., May 15, 2006; 20(10): 1218 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Khalid, S Finkelstein, B Thompson, L Kelly, C Hanck, T E Godfrey, and D C Whitcomb A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance Gut, May 1, 2006; 55(5): 728 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Juuti, J Louhimo, S Nordling, A Ristimaki, and C Haglund Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer J. Clin. Pathol., April 1, 2006; 59(4): 382 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Larsson, N. Hakansson, E. Giovannucci, and A. Wolk Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst, March 15, 2006; 98(6): 407 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsubayashi, M. Canto, N. Sato, A. Klein, T. Abe, K. Yamashita, C. J. Yeo, A. Kalloo, R. Hruban, and M. Goggins DNA Methylation Alterations in the Pancreatic Juice of Patients with Suspected Pancreatic Disease Cancer Res., January 15, 2006; 66(2): 1208 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goggins Molecular Markers of Early Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4524 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Pancreatic Section Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas Gut, June 1, 2005; 54(suppl_5): v1 - v16. [Full Text] [PDF]
|
|
|
|
 |
|
 D.A. TUVESON and S.R. HINGORANI Ductal Pancreatic Cancer in Humans and Mice Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 65 - 72. [Abstract] [PDF]
|
|
|
|
|
|
D C Whitcomb Value of genetic testing in the management of pancreatitis Gut, November 1, 2004; 53(11): 1710 - 1717. [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Whitcomb Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G315 - G319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Lowenfels and P. Maisonneuve Epidemiology and Prevention of Pancreatic Cancer Jpn. J. Clin. Oncol., May 1, 2004; 34(5): 238 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gangi, J. G. Fletcher, M. A. Nathan, J. A. Christensen, W. S. Harmsen, B. S. Crownhart, and S. T. Chari Time Interval Between Abnormalities Seen on CT and the Clinical Diagnosis of Pancreatic Cancer: Retrospective Review of CT Scans Obtained Before Diagnosis Am. J. Roentgenol., April 1, 2004; 182(4): 897 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Koopmann, Z. Zhang, N. White, J. Rosenzweig, N. Fedarko, S. Jagannath, M. I. Canto, C. J. Yeo, D. W. Chan, and M. Goggins Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry Clin. Cancer Res., February 1, 2004; 10(3): 860 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K K Barman, G Premalatha, and V Mohan Tropical chronic pancreatitis Postgrad. Med. J., November 1, 2003; 79(937): 606 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Neoptolemos, D. Cunningham, H. Friess, C. Bassi, D. D. Stocken, D. M. Tait, J. A. Dunn, C. Dervenis, F. Lacaine, H. Hickey, et al. Adjuvant therapy in pancreatic cancer: historical and current perspectives Ann. Onc., May 1, 2003; 14(5): 675 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.W. M. Spanier, M. J. Bruno, W. Burke, and R. A. Pagon Genetic Testing N. Engl. J. Med., March 13, 2003; 348(11): 1066 - 1067. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hahn, B. Greenhalf, I. Ellis, M. Sina-Frey, H. Rieder, B. Korte, B. Gerdes, R. Kress, A. Ziegler, J. A. Raeburn, et al. BRCA2 Germline Mutations in Familial Pancreatic Carcinoma J Natl Cancer Inst, February 5, 2003; 95(3): 214 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Howes and J P Neoptolemos Risk of pancreatic ductal adenocarcinoma in chronic pancreatitis Gut, December 1, 2002; 51(6): 765 - 766. [Full Text] [PDF]
|
|
|
|
|
|
D Malka, P Hammel, F Maire, P Rufat, I Madeira, F Pessione, P Levy, and P Ruszniewski Risk of pancreatic adenocarcinoma in chronic pancreatitis Gut, December 1, 2002; 51(6): 849 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Simon, F. U. Weiss, K. P. Zimmer, S. Rand, B. Brinkmann, W. Domschke, and M. M. Lerch Spontaneous and Sporadic Trypsinogen Mutations in Idiopathic Pancreatitis JAMA, November 6, 2002; 288(17): 2122 - 2122. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Simon, F. U. Weiss, M. Sahin-Toth, M. Parry, O. Nayler, B. Lenfers, J. Schnekenburger, J. Mayerle, W. Domschke, and M. M. Lerch Hereditary Pancreatitis Caused by a Novel PRSS1 Mutation (Arg-122 right-arrow Cys) That Alters Autoactivation and Autodegradation of Cationic Trypsinogen J. Biol. Chem., February 8, 2002; 277(7): 5404 - 5410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Pfutzer, E Myers, S Applebaum-Shapiro, R Finch, I Ellis, J Neoptolemos, J A Kant, and D C Whitcomb Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis Gut, February 1, 2002; 50(2): 271 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Lowenfels, P. Maisonneuve, D. C. Whitcomb, M. M. Lerch, and E. P. DiMagno Cigarette Smoking as a Risk Factor for Pancreatic Cancer in Patients With Hereditary Pancreatitis JAMA, July 11, 2001; 286(2): 169 - 170. [Full Text] [PDF]
|
|
|
|
|
|
S. Kern, R. Hruban, M. A. Hollingsworth, R. Brand, T. E. Adrian, E. Jaffee, and M. A. Tempero A White Paper: The Product of a Pancreas Cancer Think Tank Cancer Res., June 1, 2001; 61(12): 4923 - 4932. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Z. Stolzenberg-Solomon, P. Pietinen, M. J. Barrett, P. R. Taylor, J. Virtamo, and D. Albanes Dietary and Other Methyl-Group Availability Factors and Pancreatic Cancer Risk in a Cohort of Male Smokers Am. J. Epidemiol., April 1, 2001; 153(7): 680 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Tersmette, G. M. Petersen, G. J. A. Offerhaus, F. C. Falatko, K. A. Brune, M. Goggins, E. Rozenblum, R. E. Wilentz, C. J. Yeo, J. L. Cameron, et al. Increased Risk of Incident Pancreatic Cancer Among First-degree Relatives of Patients with Familial Pancreatic Cancer Clin. Cancer Res., March 1, 2001; 7(3): 738 - 744. [Abstract] [Full Text]
|
|
|
|
|
|
E EFTHIMIOU, T CRNOGORAC-JURCEVIC, N R LEMOINE, and T A BRENTNALL Inherited predisposition to pancreatic cancer Gut, February 1, 2001; 48(2): 143 - 147. [Full Text] [PDF]
|
|
|
|
|
|
N Howes, W Greenhalf, S Rutherford, M O'Donnell, R Mountford, I Ellis, D Whitcomb, C Imrie, B Drumm, and J P Neoptolemos A new polymorphism for the RI22H mutation in hereditary pancreatitis Gut, February 1, 2001; 48(2): 247 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hruban, M. Goggins, J. Parsons, and S. E. Kern Progression Model for Pancreatic Cancer Clin. Cancer Res., August 1, 2000; 6(8): 2969 - 2972. [Full Text]
|
|
|
|
|
|
A. B. Lowenfels and P. Maisonneuve Re: Maternal Inheritance Pattern of Hereditary Pancreatitis in Patients With Pancreatic Carcinoma J Natl Cancer Inst, September 15, 1999; 91(18): 1590 - 1590. [Full Text] [PDF]
|
|
|
|
|
|
M. M. Lerch, I. Ellis, D. C. Whitcomb, V. Keim, P. Simon, N. Howes, S. Rutherford, W. Domschke, C. Imrie, and J. P. Neoptolemos Maternal Inheritance Pattern of Hereditary Pancreatitis in Patients With Pancreatic Carcinoma J Natl Cancer Inst, April 21, 1999; 91(8): 723 - 724. [Full Text] [PDF]
|
|
|
|
|
|
R. Z. Stolzenberg-Solomon, D. Albanes, F. J. Nieto, T. J. Hartman, J. A. Tangrea, M. Rautalahti, J. Sehlub, J. Virtamo, and P. R. Taylor Pancreatic Cancer Risk and Nutrition-Related Methyl-Group Availability Indicators in Male Smokers J Natl Cancer Inst, March 17, 1999; 91(6): 535 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Teich, J Mossner, and V Keim Screening for mutations of the cationic trypsinogen gene: are they of relevance in chronic alcoholic pancreatitis? Gut, March 1, 1999; 44(3): 413 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I Nishimori, M Kamakura, K Fujikawa-Adachi, M Morita, S Onishi, K Yokoyama, I Makino, H Ishida, M Yamamoto, S Watanabe, et al. Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis Gut, February 1, 1999; 44(2): 259 - 263. [Abstract] [Full Text] [PDF]
|
|