Predicting and Preventing Hereditary Colorectal Cancer

Ford, James M.; Whittemore, Alice S.

doi:10.1001/jama.296.12.1521

Cited by 16 publications

(9 citation statements)

References 20 publications

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“…Interest in the Lynch syndrome has been recently addressed in a series of papers dealing with its diagnosis, molecular genetics, screening, and management, in the Journal of the American Medical Association [4][5][6][7]. Specifically, Chen et al [4] focused upon the identification of families at high risk through development and validation of a tool for genetic counseling and risk prediction which is referred to as MMRpro.…”

Section: Cancer Controlmentioning

confidence: 99%

“…Ford and Whittemore [7], in their editorial on these papers, gave appropriate emphasis to the preventive potential in the Lynch syndrome through the employment of molecular diagnostics in the hands of knowledgeable physicians and well-educated patients, so that intensive surveillance and diagnostic and prevention schemes could be employed effectively. This goal could then be abetted through the involvement of well-informed cancer genetic counselors and cancer assessment clinics [7].…”

Section: Cancer Controlmentioning

confidence: 99%

“…This goal could then be abetted through the involvement of well-informed cancer genetic counselors and cancer assessment clinics [7].…”

Section: Cancer Controlmentioning

confidence: 99%

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Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

et al. 2007

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Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family physician, oncology specialist, genetic counselor, and cancer geneticist must know fully the complexity of hereditary cancer syndromes, their differential diagnosis, in order to establish a diagnosis, direct highly-targeted surveillance and management, and then be able to communicate effectively with the molecular geneticist so that an at-risk patient's DNA can be tested in accord with the syndrome of concern. Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing. However, other germline mutations, yet to be identified, may be important should testing for these mutations prove to be absent and, therein, unrewarding to the patient. Nevertheless, our position is that if the patient's family history is consistent with one of these syndromes, but a mutation is not found in the family, we still recommend the same surveillance and management strategies for patients from families with an established cancer-causing germline mutation. Our purpose in this paper is to provide a concise coverage of the major hereditary colorectal cancer syndromes, to discuss genetic counseling, molecular genetic evaluation, highly targeted surveillance and management, so that cancer control can be maximized for these high hereditary cancer risk patients.

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Section: Cancer Controlmentioning

confidence: 99%

Section: Cancer Controlmentioning

confidence: 99%

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Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

et al. 2007

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“…For example, the United States Surgeon General was concerned enough to launch a campaign promoting awareness of the medical value of family history and encouraging data collection and analysis [9,10]. A series of papers dealing with LS diagnosis, molecular genetic screening, and management has been published [11][12][13][14], prompting advances in the knowledge of hereditary CRC, highlighting LS [6,7]. ciated with improved disease-free survival.…”

Section: Frequency Of Lynch Syndromementioning

confidence: 99%

Lynch Syndrome: Its Phenotypic and Genotypic Heterogeneity

Lynch¹,

Lynch

Gatalica

et al. 2011

Viszeralmedizin

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It is estimated that approximately 3–5% of all colorectal cancers may manifest the Lynch syndrome while its familial adenomatous polyposis counterpart accounts for less than 1% of the total colorectal cancer burden. Familial aggregation constitutes approximately 20% of all colorectal cancer occurrences. What does this mean to the geneticist, diagnostician, and ultimately the high-risk patient? Clearly, family history is the key, and when germline pathogenic mutations are identified within a family, one is then in the enviable position of providing a significant reduction in patients’ cancer morbidity and mortality through highly-targeted screening and management. Confounders for each high-risk family will be the syndrome’s phenotypic and genotypic heterogeneity, and therein it will be best comprehended through study of its natural history. In some cases the syndrome’s complexity may be beyond the physician’s knowledge, and help will then be available through referral to genetic counselors or centers of cancer genetics expertise. Finally, basic science and clinical studies on high-risk families harbor enormous opportunities to uncover etiology and pathogenesis which may ultimately translate into cancer prevention in both hereditary and sporadic forms of cancer.

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“…However, in this regard, the role and implications for MSI remain unresolved, and although consensus is evolving, suggestions to improve diagnostic accuracy and cost-effectiveness vary [57,[84][85][86][87][88][89] . The current problem with family history alone (the Amsterdam criteria, original and revised; table 4 ) is that it does not catch all carriers (i.e.…”

Section: Differences In Microsatellite Dinucleotides (Type a And B Chmentioning

confidence: 99%

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Søreide

2007

Tumor Biol

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Microsatellite instability (MSI) is a genetic feature of colorectal cancer (CRC) associated with peculiar clinicopathological features and improved prognosis. It is demonstrated in >90% of patients with hereditary non-polyposis colorectal cancer (HNPCC) in which DNA mismatch repair (MMR) defects are the cause of MSI. HNPCC develop at a young age, and patients are at increased risk for additional cancers (e.g. endometrial, stomach, or biliary tract cancer). MSI is found in 15–20% of sporadic CRC, often based on epigenetic silencing (i.e. MLH1). The prognostic and predictive value of MSI is not yet fully elucidated, although improved survival in MSI is suggested. Distinguishing sporadic MSI from HNPCC is at present guided by the combination of familial history, immunohistochemistry, and genotyping of MMR genes (MLH1, MSH2, MSH6, and PMS2). The efficiency and accuracy of MSI testing is evolving, with more knowledge achieved concerning multipopulation polymorphisms, selection of markers (e.g. quasimonomorphic vs. dinucleotides), and more time-efficient panels (e.g. not requiring normal/germline DNA match). The role of distinct genetic features, such as BRAF V600E mutations often found in sporadic MSI but not in HNPCC, may further improve future test algorithms. The present knowledge and controversies pertaining to molecular testing of MSI and MMR defects in CRC are presented.

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Predicting and Preventing Hereditary Colorectal Cancer

Cited by 16 publications

References 20 publications

Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

Lynch Syndrome: Its Phenotypic and Genotypic Heterogeneity

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

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Predicting and Preventing Hereditary Colorectal Cancer

Cited by 16 publications

References 20 publications

Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

Lynch Syndrome: Its Phenotypic and Genotypic Heterogeneity

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers &ndash; Ready for Prime Time?

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Product

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Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?