Hereditary pancreatitis and the risk of pancreatic cancer

Albert B. Lowenfels, Patrick Maisonneuve, Eugene P. DiMagno, Yoram Elitsur, Lawrence K. Gates, Jean Perrault, David C. Whitcomb

Research output: Contribution to journalArticle

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Abstract

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 (≤130 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.

Original languageEnglish
Pages (from-to)442-446
Number of pages5
JournalJournal of the National Cancer Institute
Volume89
Issue number6
Publication statusPublished - Mar 19 1997

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Pancreatic Neoplasms
Pancreatitis
Trypsinogen
Inheritance Patterns
Hereditary pancreatitis
Chronic Pancreatitis
Genes
Incidence
Confidence Intervals
Neoplasms
Penetrance
Natural History
Abdominal Pain
Medical Records
Longitudinal Studies
Cause of Death
Adenocarcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lowenfels, A. B., Maisonneuve, P., DiMagno, E. P., Elitsur, Y., Gates, L. K., Perrault, J., & Whitcomb, D. C. (1997). Hereditary pancreatitis and the risk of pancreatic cancer. Journal of the National Cancer Institute, 89(6), 442-446.

Hereditary pancreatitis and the risk of pancreatic cancer. / Lowenfels, Albert B.; Maisonneuve, Patrick; DiMagno, Eugene P.; Elitsur, Yoram; Gates, Lawrence K.; Perrault, Jean; Whitcomb, David C.

In: Journal of the National Cancer Institute, Vol. 89, No. 6, 19.03.1997, p. 442-446.

Research output: Contribution to journalArticle

Lowenfels, AB, Maisonneuve, P, DiMagno, EP, Elitsur, Y, Gates, LK, Perrault, J & Whitcomb, DC 1997, 'Hereditary pancreatitis and the risk of pancreatic cancer', Journal of the National Cancer Institute, vol. 89, no. 6, pp. 442-446.
Lowenfels AB, Maisonneuve P, DiMagno EP, Elitsur Y, Gates LK, Perrault J et al. Hereditary pancreatitis and the risk of pancreatic cancer. Journal of the National Cancer Institute. 1997 Mar 19;89(6):442-446.
Lowenfels, Albert B. ; Maisonneuve, Patrick ; DiMagno, Eugene P. ; Elitsur, Yoram ; Gates, Lawrence K. ; Perrault, Jean ; Whitcomb, David C. / Hereditary pancreatitis and the risk of pancreatic cancer. In: Journal of the National Cancer Institute. 1997 ; Vol. 89, No. 6. pp. 442-446.
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abstract = "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 (≤130 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.",
author = "Lowenfels, {Albert B.} and Patrick Maisonneuve and DiMagno, {Eugene P.} and Yoram Elitsur and Gates, {Lawrence K.} and Jean Perrault and Whitcomb, {David C.}",
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TY - JOUR

T1 - Hereditary pancreatitis and the risk of pancreatic cancer

AU - Lowenfels, Albert B.

AU - Maisonneuve, Patrick

AU - DiMagno, Eugene P.

AU - Elitsur, Yoram

AU - Gates, Lawrence K.

AU - Perrault, Jean

AU - Whitcomb, David C.

PY - 1997/3/19

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N2 - 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 (≤130 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.

AB - 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 (≤130 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.

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