Evolution of the Nomenclature for the Hereditary Colorectal Cancer Syndromes

Boland, C. Richard

doi:10.1007/s10689-004-4489-x

Cited by 114 publications

(79 citation statements)

References 67 publications

(63 reference statements)

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“…It is also commonly known as hereditary nonpolyposis colorectal cancer (HNPCC), which may be a misnomer because cancer predisposition is not restricted to the colon. The term Lynch syndrome has been specifically referred to as individuals diagnosed based on an inherited germ-line mutation in a DNA MMR gene (2,3) and has been used as such herein. Many types of cancer cluster in families with Lynch syndrome.…”

Section: Introductionmentioning

confidence: 99%

Influence ofMethylenetetrahydrofolate ReductaseGene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population

Pande¹,

Chen²,

Amos³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Lynch syndrome is caused by germ-line mutations in the DNA mismatch repair (MMR) genes; mutation carriers are predisposed to a variety of cancers, most commonly colorectal and endometrial. The median age of colorectal cancer onset is 45 years and the lifetime risk is f80%, but the onset age varies substantially. It is likely that other low-penetrance genes and environmental factors act as modifiers of the risk associated with the highly penetrant MMR gene mutations. Methylenetetrahydrofolate reductase plays a key role in folate metabolism. We investigated the association of C677T and A1298C, two common polymorphisms in the methylenetetrahydrofolate reductase gene, with risk for early onset colorectal cancer in Lynch syndrome. Subjects were 185 non-Hispanic whites with confirmed DNA MMR mutations. Kaplan-Meier estimates for the age at colorectal cancer onset according to C677T genotypes were significantly different for the CT and TT genotypes compared with the wild-type CC (P = 0.014, log-rank test; P = 0.004, trend test). The median ages at onset were 43 years for the CC genotype and 39 years for the combined CC and CT genotypes and the CC+CT genotypes were associated with a reduced age-associated risk for developing colorectal cancer (hazard ratio, 0.55; 95% confidence interval, 0.36-0.85). No differences in ages at onset or risk were found for the A1298C genotypes. This is the first report to our knowledge to provide evidence that the C677T polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect.

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Section: Introductionmentioning

confidence: 99%

Influence ofMethylenetetrahydrofolate ReductaseGene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population

Pande¹,

Chen²,

Amos³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The term Lynch syndrome (LS) is now favored over hereditary nonpolyposis colorectal cancer, however, because the syndrome-associated cancers are not restricted to the colon and the syndrome is now formally defined by genotype (ie, a germline MMR gene defect) rather than a specific phenotype. 6 Extracolonic sites for cancer in LS include the endometrium, small bowel, hepatobiliary tract, uroepithelium of the renal pelvis, ureter, and pancreas. 7,8 The Turcot variant of LS is characterized by malignant brain tumors (astrocytoma and glioblastoma) in addition to other syndrome-associated cancers, and the Muir-Torre variant is characterized by multiple benign and malignant sebaceous tumors and keratoacanthomas in addition to other syndrome-associated cancers.…”

mentioning

confidence: 99%

“…10 As currently defined, LS pertains only to those individuals in whom a germline mutation in an MMR gene is identified. 6 A new term, familial colorectal cancer type X, refers to individuals who meet the Amsterdam criteria but show no evidence of an MMR gene defect.…”

mentioning

confidence: 99%

Microsatellite Instability and Colorectal Cancer

Geiersbach¹,

Samowitz²

2011

Archives of Pathology &Amp; Laboratory Medicine

121

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Context.—About 15% of colorectal cancers are characterized by genomic microsatellite instability, and of these, about 1 in 5 (2%–4% overall) are due to Lynch syndrome, a dominantly inherited condition predisposing the patient to cancers of multiple organ systems, including the gastrointestinal tract. Identification of individuals with Lynch syndrome allows for increased surveillance of the affected individual and of potentially affected family members. Objective.—To review the literature on microsatellite instability in colorectal cancer and current laboratory diagnostic testing strategies for the detection of Lynch syndrome. Data Sources.—This review is based on peer-reviewed literature, published guidelines from professional organizations (Evaluation of Genomic Applications in Practice and Prevention Working Group, National Comprehensive Cancer Network), and information from clinical laboratories performing microsatellite instability testing. Conclusions.—Universal screening for Lynch syndrome in all individuals affected with colorectal cancer has been recommended by the Evaluation of Genomic Applications in Practice and Prevention Working Group. Preliminary screening tests can identify individuals unlikely to be affected by Lynch syndrome, thereby reducing the need for full gene analysis. Immunohistochemistry and polymerase chain reaction–based tests for microsatellite instability have similar clinical sensitivity and specificity, and each method has advantages and limitations. BRAF and MLH1 methylation testing are useful reflex tests for those with a defect in MLH1 identified by immunohistochemistry. Emerging technologies, such as high-throughput sequencing, may substantially affect diagnostic algorithms in the future.

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“…These criteria have been expanded to include extra-colonic malignancies and other risk factors for genetic disease (Amsterdam II and Bethesda criteria) (4,5). The term Lynch syndrome has been suggested as more appropriate than HNPCC as this name clarifies the consideration of noncolonic cancers in a family history and unifies the diagnosis around the germline mutation in a DNA mismatch repair gene (6). It is well known that not all HNPCC defined families (Amsterdam-positive criteria) have true Lynch syndrome and in many cases MSI of tumors exist without vertical transmission of an aberrant DNA mismatch repair gene.…”

Section: Introductionmentioning

confidence: 99%

Clustering of Lynch syndrome malignancies with no evidence for a role of DNA mismatch repair

Case

Zighelboim

Mutch

et al. 2008

Gynecologic Oncology

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Objectives-We ascertained a large kindred with an excess of Lynch syndrome-associated cancers. Our objective was to determine if a defect in one of the DNA mismatch repair (DMMR) genes was the probable cause of cancer susceptibility as microsatellite instability (MSI) and immunohistochemical (IHC) analysis of the probands' tumors did not provide a clear indication.Methods-A detailed history and review of medical records was undertaken to construct a fourgeneration pedigree. Blood samples were obtained for analysis of germline DNA. Polymorphic repeats from the MLH1, MSH2, MSH6, and PMS2 loci were genotyped and the co-segregation of markers and disease was assessed. DMMR gene expression for all available tumors was evaluated by IHC. Combined bisulfite restriction analysis (COBRA) of MLH1 was utilized to test for germline epimutation.Results-Four gynecologic carcinomas, 3 colon carcinomas, and 13 cases of adenomatous polyps were identified. The family met Amsterdam II criteria. The mean age of cancer diagnosis in the kindred was 63 years (range 44-82). DNA marker analyses excluded linkage to MLH1, MSH2, MSH6, and PMS2. Furthermore, MSI and IHC analysis of tumors did not suggest a role for DMMR. Methylation of the MLH1 promoter was identified in the peripheral blood leukocytes (PBLs) of a family member with an early onset colon cancer.Conclusions-We identified a large family with multiple Lynch malignancies and no evidence for an inherited defect in DMMR. This family represents an important but poorly understood form of autosomal dominant inherited cancer susceptibility. Aberrant MLH1 promoter methylation in normal tissues may be a marker for cancer susceptibility in families such as this.

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Evolution of the Nomenclature for the Hereditary Colorectal Cancer Syndromes

Cited by 114 publications

References 67 publications

Influence ofMethylenetetrahydrofolate ReductaseGene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population

Influence ofMethylenetetrahydrofolate ReductaseGene Polymorphisms C677T and A1298C on Age-Associated Risk for Colorectal Cancer in a Caucasian Lynch Syndrome Population

Microsatellite Instability and Colorectal Cancer

Clustering of Lynch syndrome malignancies with no evidence for a role of DNA mismatch repair

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