Hereditary nonpolyposis colorectal cancer (HNPCC), also referred to as Lynch syndromes I and II, is an autosomal, dominantly inherited disorder that accounts for approximately 5% of all colorectal cancers. While colorectal cancer is the most frequently occurring malignancy in HNPCC, other types of cancer occur with increased statistical significance. A better understanding of its natural history, particularly early age of onset and the pattern of multiple primary cancer excess, is essential for the diagnosis and management of HNPCC.
Get full access to this article
View all access options for this article.
References
1.
WingoP.A., TongT., BoldenS.Cancer statistics, 1995. CA Cancer J Clin.1995; 45: 8–30.
2.
WatsonP., LynchH.T.Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer.1993; 71: 677–685.
3.
LynchH.T., SmyrkT.C., WatsonP.Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology.1993; 104: 1535–1549.
4.
MecklinJ.P., JarvinenH.J., HakkiluotoA.Frequency of hereditary nonpolyposis colorectal cancer: a prospective multicenter study in Finland. Dis Colon Rectum.1995; 38: 588–593.
5.
Nystrom-LahtiM., SistonenP., MecklinJ.P.Close linkage to chromosome 3p and conservation of ancentral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc Natl Acad Sci U S A.1994; 91: 6054–6058.
6.
PeltomakiP., AaltonenL.A., SistonenP.Genetic mapping of a locus predisposing to human colorectal cancer. Science.1993; 260: 810–812.
7.
LindblomA., TannergardP., WereliusB.Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet.1993; 5: 279–282.
8.
LeachF.S., NicolaidesN.C., PapadopoulosN.Mutations of a MutS homolog in hereditary nonpolyposis colorectal cancer. Cell.1993; 75: 1215–1225.
9.
FishelR., LescoeM.K., RaoM.R.The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell.1993; 75: 1027–1038.
10.
PapadopoulosN., NicolaidesN.C., WeiY.F.Mutation of a mutL homolog in hereditary colon cancer. Science.1994; 263: 1625–1629.
11.
BronnerC.E., BakerS.M., MorrisonP.T.Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature.1994; 368: 258–261.
12.
LiuB., ParsonsR.E., HamiltonS.R.hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res.1994; 54: 4590–4594.
13.
NicolaidesN.C., PapadopoulosN., LiuB.Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature.1994; 371: 75–80.
14.
LoveR.R.Adenomas are precursor lesions for malignant growth in nonpolyposis hereditary carcinoma of the colon and rectum. Surg Gynecol Obstet.1986; 162: 8–12.
15.
JarvinenH.J., MecklinJ.P., SistonenP.Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology.1995; 108: 1405–1411.
16.
JassJ.R., YoungP.J., RobinsonE.M.Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas: a necropsy study in New Zealand. Gut.1992; 33: 1508–1514.
17.
JassJ.R., StewartS.M., StewartJ.Hereditary non-polyposis colorectal cancer: morphologies, genes and mutations. Mutat Res.1994; 310: 125–133.
18.
JacobyR.F., MarshallD.F., KailasS.Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer. Gastroenterology.1995; 109: 73–82.
19.
HemminkiA., PeltomakiP., MecklinJ.P.Loss of the wild type MLH1 gene is a feature of hereditary nonpolyposis colorectal cancer. Nat Genet.1994; 8: 405–410.
20.
IchiiS., HoriiA., NakatsuruS.Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP). Hum Mol Genet.1992; 1: 387–390.
21.
AaltonenL.A., PeltomakiP.S., MecklinJ.P.Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res.1994; 54: 1645–1648.
22.
AaltonenL.A., PeltomakiP., LeachF.S.Clues to the pathogenesis of familial colorectal cancer. Science.1993; 260: 812–816.
23.
YoungJ., LeggettB., GustafsonC.Genomic instability occurs in colorectal carcinomas but not in adenomas. Hum Mutat.1993; 2: 351–354.
24.
VasenH.F., NagengastF.M., KhanP.M.Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome). Lancet.1995; 345: 1183–1184.
25.
WinawerS.J., ZauberA.G., O'BrienM.J.National Polyp Study Workgroup. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. N Engl J Med.1993; 328: 901–906.
26.
WinawerS.J., ZauberA.G., HoM.N.National Polyp Study Workgroup. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med.1993; 329: 1977–1981.
27.
AlbanoW.A., RecabarenJ.A., LynchH.T.Natural history of hereditary cancer of the breast and colon. Cancer.1982; 50: 360–363.
28.
LoveR.R., MorisseyJ.F.Colonoscopy in asymptomatic individuals with a family history of colorectal cancer. Arch Intern Med.1984; 144: 2209–2211.
29.
ShibataD., PeinadoM.A., IonovY.Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet.1994; 6: 273–281.
30.
MizoguchiH., O'SheaJ.J., LongoD.L.Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science.1992; 258: 1795–1798.
31.
LynchH.T.Dynamic Genetic Counseling for Clinicians.Springfield, Ill: CC Thomas; 1969.
32.
SchneiderK.A.Counseling About Cancer: Strategies for Genetic Counselors.Wallingford, Pa: NSGC Executive Office; 1994.
33.
LynchH.T., LynchP.M., PesterJ.The cancer family syndrome: rare cutaneous phonotypic linkage of Torre1s syndrome. Arch Intern Med.1981; 141: 607–611.
34.
LynchH.T., FusaroR.M., RobertsL.Muir-Torre syndrome in several members of a family with a variant of the cancer family syndrome. Br J Dermatol.1985; 113: 295–301.
35.
PetersenG.M., FrancomanoC., KinzlerK.Presymptomatic direct detection of adenomatous polyposis coli (APC) gene mutations in familial adenomatous polyposis. Hum Genet.1993; 91: 307–311.
36.
Presymptomatic testing for Huntington's disease: a world wide survey.The World Federation of Neurology Research Group on Huntington's disease. J Med Genet.1993; 30: 1020–1022.
37.
ThiesU., BockelB., BochdalofskyV.Attitudes of neurologists, psychiatrists, and psychotherapists towards predictive testing for Huntington's disease in Germany. J Med Genet.1993; 30: 1023–1027.
38.
SimpsonS.A., HardingA.E.Predictive testing for Huntington's disease: after the gene. The United Kingdom Huntington's Disease Prediction Consortium. J Med Genet.1993; 30: 1036–1038.
39.
ArvanitisM.L., JagelmanD.G., FazioV.N.Mortality in patients with familial adenomatous polyposis. Dis Colon Rectum.1990; 33: 639–642.
