Challenging pancreatic cancer-prone pedigrees

A nosologic dilemma

Henry T. Lynch, Carolyn A. Deters, Jane F. Lynch, Randall A. Brand

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

OBJECTIVES: Our objective is to describe 11 pancreatic cancer (PC)-prone families, none of which are consonant with known hereditary cancer syndromes, in an attempt to portray familial aggregations of this disease that might be encountered in a clinical practice setting. METHODS: We selected 11 families containing two or more first- and/or second-degree relatives affected with PC from a registry of 200 PC-prone kindreds. Each proband and/or key relative(s) was interviewed and completed a detailed family history questionnaire (after providing informed consent) that allowed us to extend the pedigree as far as possible with retrieval of primary medical and pathology documents, whenever available. RESULTS: All of the 11 families show PC features that merit clinical attention and raise questions as to whether this familial clustering could be due to "chance" alone, exposure to certain common environmental factors, such as cigarette smoking, and/or polygenic, multifactorial, or Mendelian inherited factors. CONCLUSIONS: It is estimated that about 5% of PC may have a primary hereditary etiology. Because of early death, reduced penetrance, and often profuse phenotypic and genotypic heterogeneity, particularly with respect to variable age of onset and association with diverse patterns of cancer at different anatomic sites, the pedigrees require extension for ultimate diagnosis. Physician knowledge about PC's natural history and syndrome delineation should ultimately foster earlier diagnoses and possibly prevention of this disease. These high-risk patients may provide a source of DNA for formal linkage analysis in the search for culprit cancer-prone susceptibility loci.

Original languageEnglish
Pages (from-to)3062-3070
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume97
Issue number12
DOIs
StatePublished - Dec 1 2002

Fingerprint

Pedigree
Pancreatic Neoplasms
Hereditary Neoplastic Syndromes
Penetrance
Natural History
Informed Consent
Age of Onset
Cluster Analysis
Registries
Early Diagnosis
Neoplasms
Smoking
Pathology
Physicians
DNA

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Challenging pancreatic cancer-prone pedigrees : A nosologic dilemma. / Lynch, Henry T.; Deters, Carolyn A.; Lynch, Jane F.; Brand, Randall A.

In: American Journal of Gastroenterology, Vol. 97, No. 12, 01.12.2002, p. 3062-3070.

Research output: Contribution to journalArticle

Lynch, Henry T. ; Deters, Carolyn A. ; Lynch, Jane F. ; Brand, Randall A. / Challenging pancreatic cancer-prone pedigrees : A nosologic dilemma. In: American Journal of Gastroenterology. 2002 ; Vol. 97, No. 12. pp. 3062-3070.
@article{873e3fbcb21640f692b58795b2050131,
title = "Challenging pancreatic cancer-prone pedigrees: A nosologic dilemma",
abstract = "OBJECTIVES: Our objective is to describe 11 pancreatic cancer (PC)-prone families, none of which are consonant with known hereditary cancer syndromes, in an attempt to portray familial aggregations of this disease that might be encountered in a clinical practice setting. METHODS: We selected 11 families containing two or more first- and/or second-degree relatives affected with PC from a registry of 200 PC-prone kindreds. Each proband and/or key relative(s) was interviewed and completed a detailed family history questionnaire (after providing informed consent) that allowed us to extend the pedigree as far as possible with retrieval of primary medical and pathology documents, whenever available. RESULTS: All of the 11 families show PC features that merit clinical attention and raise questions as to whether this familial clustering could be due to {"}chance{"} alone, exposure to certain common environmental factors, such as cigarette smoking, and/or polygenic, multifactorial, or Mendelian inherited factors. CONCLUSIONS: It is estimated that about 5{\%} of PC may have a primary hereditary etiology. Because of early death, reduced penetrance, and often profuse phenotypic and genotypic heterogeneity, particularly with respect to variable age of onset and association with diverse patterns of cancer at different anatomic sites, the pedigrees require extension for ultimate diagnosis. Physician knowledge about PC's natural history and syndrome delineation should ultimately foster earlier diagnoses and possibly prevention of this disease. These high-risk patients may provide a source of DNA for formal linkage analysis in the search for culprit cancer-prone susceptibility loci.",
author = "Lynch, {Henry T.} and Deters, {Carolyn A.} and Lynch, {Jane F.} and Brand, {Randall A.}",
year = "2002",
month = "12",
day = "1",
doi = "10.1016/S0002-9270(02)05519-3",
language = "English",
volume = "97",
pages = "3062--3070",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Challenging pancreatic cancer-prone pedigrees

T2 - A nosologic dilemma

AU - Lynch, Henry T.

AU - Deters, Carolyn A.

AU - Lynch, Jane F.

AU - Brand, Randall A.

PY - 2002/12/1

Y1 - 2002/12/1

N2 - OBJECTIVES: Our objective is to describe 11 pancreatic cancer (PC)-prone families, none of which are consonant with known hereditary cancer syndromes, in an attempt to portray familial aggregations of this disease that might be encountered in a clinical practice setting. METHODS: We selected 11 families containing two or more first- and/or second-degree relatives affected with PC from a registry of 200 PC-prone kindreds. Each proband and/or key relative(s) was interviewed and completed a detailed family history questionnaire (after providing informed consent) that allowed us to extend the pedigree as far as possible with retrieval of primary medical and pathology documents, whenever available. RESULTS: All of the 11 families show PC features that merit clinical attention and raise questions as to whether this familial clustering could be due to "chance" alone, exposure to certain common environmental factors, such as cigarette smoking, and/or polygenic, multifactorial, or Mendelian inherited factors. CONCLUSIONS: It is estimated that about 5% of PC may have a primary hereditary etiology. Because of early death, reduced penetrance, and often profuse phenotypic and genotypic heterogeneity, particularly with respect to variable age of onset and association with diverse patterns of cancer at different anatomic sites, the pedigrees require extension for ultimate diagnosis. Physician knowledge about PC's natural history and syndrome delineation should ultimately foster earlier diagnoses and possibly prevention of this disease. These high-risk patients may provide a source of DNA for formal linkage analysis in the search for culprit cancer-prone susceptibility loci.

AB - OBJECTIVES: Our objective is to describe 11 pancreatic cancer (PC)-prone families, none of which are consonant with known hereditary cancer syndromes, in an attempt to portray familial aggregations of this disease that might be encountered in a clinical practice setting. METHODS: We selected 11 families containing two or more first- and/or second-degree relatives affected with PC from a registry of 200 PC-prone kindreds. Each proband and/or key relative(s) was interviewed and completed a detailed family history questionnaire (after providing informed consent) that allowed us to extend the pedigree as far as possible with retrieval of primary medical and pathology documents, whenever available. RESULTS: All of the 11 families show PC features that merit clinical attention and raise questions as to whether this familial clustering could be due to "chance" alone, exposure to certain common environmental factors, such as cigarette smoking, and/or polygenic, multifactorial, or Mendelian inherited factors. CONCLUSIONS: It is estimated that about 5% of PC may have a primary hereditary etiology. Because of early death, reduced penetrance, and often profuse phenotypic and genotypic heterogeneity, particularly with respect to variable age of onset and association with diverse patterns of cancer at different anatomic sites, the pedigrees require extension for ultimate diagnosis. Physician knowledge about PC's natural history and syndrome delineation should ultimately foster earlier diagnoses and possibly prevention of this disease. These high-risk patients may provide a source of DNA for formal linkage analysis in the search for culprit cancer-prone susceptibility loci.

UR - http://www.scopus.com/inward/record.url?scp=0036895979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036895979&partnerID=8YFLogxK

U2 - 10.1016/S0002-9270(02)05519-3

DO - 10.1016/S0002-9270(02)05519-3

M3 - Article

VL - 97

SP - 3062

EP - 3070

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 12

ER -