TY - JOUR
T1 - Colon cancer genetics
AU - Lynch, Henry T.
AU - Watson, Patrice
AU - Smyrk, Thomas C.
AU - Lanspa, Stephen J.
AU - Boman, Bruce M.
AU - Boland, C. Richard
AU - Lynch, Jane F.
AU - Cavalieri, R. Jennifer
AU - Lepperf, Mark
AU - White, Ray
AU - Sidransky, David
AU - Vogelstein, Bert
PY - 1992/9/1
Y1 - 1992/9/1
N2 - The terms “hereditary,” “sporadic,” and “familial” colorectal cancer (CRC) suggest a knowledge of causation; however, current understanding of CRC does not permit categorization of differing CRC risks in accord with their cause per se. Despite these serious shortcomings, these terms are defined operationally on the basis of a family history of cancer, and when available, additional phenotypic information. The sporadic type occurs in the absence of a family history of CRC in a first‐degree relative. The familial type occurs when at least one first‐degree relative has CRC. Both these categories require the exclusion of hereditary CRC. In the case of hereditary CRC, this type is defined as a family history of CRC occurring in a pattern that indicates autosomal‐dominant inheritance, which also may involve certain phenotypic signs (depending on the specific disorder, i.e., florid adenoma‐tous polyps, benign and malignant extracolonic lesions, cancer of unusually early onset, and multiple primary cancer, particularly synchronous and metachronous CRC). Although this operational classification does not produce etiologically homogeneous groups, it is believed to have pragmatic utility with respect to planning targeted surveillance and management strategies. Because of the distinctive natural history of CRC in hereditary syndromes, it is of paramount clinical importance to identify hereditary CRC when it does occur. Even in patients with no evidence of hereditary CRC syndrome, their family history may be second only to age in determining the best CRC screening program for those who are asymptomatic. In an attempt to provide a perspective on the clinical evaluation of CRC risk, research was reviewed on pathologic features and biomarkers that may be related to CRC causes, especially the genetic basis of CRC susceptibility. The long‐term objective of studies on the genetic epidemiology of CRC is primary and secondary prevention through development of targeted management and surveillance recommendations (based on an understanding of CRC causation) that is relevant to hereditary, familial, and sporadic CRC.
AB - The terms “hereditary,” “sporadic,” and “familial” colorectal cancer (CRC) suggest a knowledge of causation; however, current understanding of CRC does not permit categorization of differing CRC risks in accord with their cause per se. Despite these serious shortcomings, these terms are defined operationally on the basis of a family history of cancer, and when available, additional phenotypic information. The sporadic type occurs in the absence of a family history of CRC in a first‐degree relative. The familial type occurs when at least one first‐degree relative has CRC. Both these categories require the exclusion of hereditary CRC. In the case of hereditary CRC, this type is defined as a family history of CRC occurring in a pattern that indicates autosomal‐dominant inheritance, which also may involve certain phenotypic signs (depending on the specific disorder, i.e., florid adenoma‐tous polyps, benign and malignant extracolonic lesions, cancer of unusually early onset, and multiple primary cancer, particularly synchronous and metachronous CRC). Although this operational classification does not produce etiologically homogeneous groups, it is believed to have pragmatic utility with respect to planning targeted surveillance and management strategies. Because of the distinctive natural history of CRC in hereditary syndromes, it is of paramount clinical importance to identify hereditary CRC when it does occur. Even in patients with no evidence of hereditary CRC syndrome, their family history may be second only to age in determining the best CRC screening program for those who are asymptomatic. In an attempt to provide a perspective on the clinical evaluation of CRC risk, research was reviewed on pathologic features and biomarkers that may be related to CRC causes, especially the genetic basis of CRC susceptibility. The long‐term objective of studies on the genetic epidemiology of CRC is primary and secondary prevention through development of targeted management and surveillance recommendations (based on an understanding of CRC causation) that is relevant to hereditary, familial, and sporadic CRC.
KW - biomarkers
KW - colon cancer genetics
KW - family history
KW - heterogeneity
UR - http://www.scopus.com/inward/record.url?scp=0026744757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026744757&partnerID=8YFLogxK
U2 - 10.1002/1097-0142(19920901)70:3+<1300::AID-CNCR2820701517>3.0.CO;2-O
DO - 10.1002/1097-0142(19920901)70:3+<1300::AID-CNCR2820701517>3.0.CO;2-O
M3 - Article
C2 - 1511377
AN - SCOPUS:0026744757
SN - 0008-543X
VL - 70
SP - 1300
EP - 1312
JO - Cancer
JF - Cancer
IS - 3 S
ER -