Detecting hereditary nonpolyposis colorectal cancer syndrome (HNPCC) in patients with colorectal cancer (CRC): Optimal strategies at lower costs.

396 Background: The optimal strategy to detect HNPCC in CRC pts remains controversial, and may include testing tumors for microsatellite (MSI) status and/or pts for mutations in DNA mismatch repair (MMR) genes. Costs of 6 testing strategies were compared against their risks of missing pt managed as HNPCC. Methods: 185 consecutive CRCs were prospectively tested by both immunohistochemistry (IHC, for protein expressions of MLH1, MSH2, MSH6, PMS2) and PCR-based MSI. Secondary tests included MLH1 promoter methylation, BRAF mutation, and germline mutation, as appropriate. A decision tree compared the strategy of performing both IHC and MSI in all (Strategy 1) to five alternatives (Strategies 2-6, Table ). Costs were obtained from commercial list prices, Medicare reimbursement, and literature; probabilities were calculated from pt data. Incremental cost-effectiveness ratios (ICERs) were reported for each additional pt managed as HNPCC Results: 20 (10.8%) pts were identified as being managed as HNPCC. Performing IHC and MSI in all (Strategy 1) or IHC first in all followed by MSI when IHC was normal (Strategy 4) detected all 20 cases. When compared to performing IHC only (Strategy 2), Strategy 4 demonstrated an ICER of $31,821 per additional case detected, while other strategies were more costly and/or less effective (Table). Between the two strategies that detected all cases of HNPCC, Strategy 4 was less costly ($1,049 vs $1,098 per patient, Table). Conclusions: When combined with appropriate secondary and confirmatory testing, performing IHC and MSI in all or IHC in all followed by MSI when IHC were normal, both showed a zero miss rate, while the latter was slightly more cost-effective. [Table: see text]

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Preventive surgery for colon cancer in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome

Langenbeck s Archives of Surgery ◽

10.1007/s00423-003-0364-8 ◽

2003 ◽

Vol 388 (1) ◽

pp. 9-16 ◽

Cited By ~ 29

Author(s):

Gabriela Möslein ◽

Steffen Pistorius ◽

Hans-Detlev Saeger ◽

Hans K. Schackert

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Familial Adenomatous Polyposis ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Adenomatous Polyposis ◽

Cancer Syndrome ◽

Preventive Surgery ◽

Hereditary Nonpolyposis

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Hereditary Nonpolyposis Colorectal Cancer Syndrome in a Patient With Urothelial Carcinoma of the Upper Urothelial Tract

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-e60-hnccsi ◽

2003 ◽

Vol 127 (2) ◽

pp. e60-e63

Author(s):

Arndt Hartmann ◽

John C. Cheville ◽

Wolfgang Dietmaier ◽

Ferdinand Hofstädter ◽

Lawrence J. Burgart ◽

...

Keyword(s):

Colorectal Cancer ◽

Urinary Tract ◽

Urothelial Carcinoma ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Upper Urinary Tract ◽

Cancer Syndrome ◽

Tract Cancer ◽

Hereditary Nonpolyposis ◽

History Of ◽

History Of Cancer

Abstract Urothelial carcinoma of the upper urinary tract is relatively uncommon but may develop as a manifestation of the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which is characterized by mutations in a number of DNA mismatch repair genes and detectable as microsatellite instability or loss of the respective protein by immunostaining. No well-established screening test is available for urothelial carcinomas of the upper urinary tract, and little is known of the clinical impact of screening for HNPCC in patients with upper urinary tract cancer. We describe herein a patient with a urothelial carcinoma of the ureter and a strongly positive history of cancer, who was subsequently found to have HNPCC. Our findings reinforce the importance of obtaining a comprehensive history of cancer in patients with urothelial carcinoma of the renal pelvis and ureter. Subsequent identification of individuals with HNPCC enables the patient and at-risk relatives to benefit from targeted surveillance and management programs.

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Recent advances in understanding Lynch syndrome

F1000Research ◽

10.12688/f1000research.9654.1 ◽

2016 ◽

Vol 5 ◽

pp. 2889 ◽

Cited By ~ 2

Author(s):

Sherief Shawki ◽

Matthew F. Kalady

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Correct Diagnosis ◽

Diagnostic Testing ◽

Gene Mutations ◽

The United States ◽

Cancer Syndrome ◽

Dna Mismatch ◽

Recent Developments ◽

Risk Patients

Colorectal cancer affects about 4.4% of the population and is a leading cause of cancer-related death in the United States. Approximately 10% to 20% of cases occur within a familial pattern, and Lynch syndrome is the most common hereditary colorectal cancer syndrome. Lynch syndrome is a hereditary predisposition to forming colorectal and extracolonic cancers, caused by a germline mutation in one of the DNA mismatch repair genes. Identifying at-risk patients and making a correct diagnosis are the keys to successful screening and interventions which will decrease formation of and death from cancers. Knowledge of the genetics and the natural history of Lynch syndrome has continued to be uncovered in recent years, leading to a better grasp on how these patients and their families should be managed. Recent developments include the approach to diagnostic testing, more precise definitions of the syndrome and risk stratification based on gene mutations, surgical decision-making, and chemoprevention.

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A Dynamic Family History model Of Hereditary Nonpolyposis Colorectal Cancer and Critical Illness Insurance

Annals of Actuarial Science ◽

10.1017/s1748499500000373 ◽

2007 ◽

Vol 2 (2) ◽

pp. 289-325 ◽

Cited By ~ 3

Author(s):

L. Lu ◽

A. S. Macdonald ◽

H. R. Waters ◽

F. Yu

Keyword(s):

Colorectal Cancer ◽

Critical Illness ◽

Family History ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Familial Aggregation ◽

Family History Information ◽

Dna Mismatch ◽

Genetic Test Results ◽

Hereditary Nonpolyposis ◽

History Of

ABSTRACTHereditary nonpolyposis colorectal cancer (HNPCC) is characterised by the familial aggregation of cancer of the colon and rectum (CRC). It may be caused by any of five mutations in DNA mismatch repair (MMR) genes or by non-genetic factors, such as life style. However, it accounts for only about 2% of CRC, which is a very common cancer. Previous actuarial models, of diseases with only genetic causes, assumed that a family history of the disease shows mutations to be present, but this is not true of HNPCC. This is a significant limitation, since the best information available to an underwriter (especially if the use of genetic test results is banned) is likely to be knowledge of a family history of CRC. We present a Markov model of CRC and HNPCC, which includes the presence of a family history of CRC as a state, and estimate its intensities allowing for MMR genotype. Using this we find the MMR mutation probabilities for an insurance applicant with a family history of CRC. Our model greatly simplifies the intensive computational burden of finding such probabilities by integrating over complex models of hidden family structure. We estimate the costs of critical illness insurance given the applicant's genotype or the presence of a family history. We then consider what the cost of adverse selection might be, if insurers are unable to use genetic tests or family history information. We also consider the effect of using alternative definitions of a family history in underwriting.

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MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1722106115 ◽

2018 ◽

Vol 115 (11) ◽

pp. 2806-2811 ◽

Cited By ~ 3

Author(s):

David W. Brammer ◽

Patrick J. Gillespie ◽

Mei Tian ◽

Daniel Young ◽

Muthuswamy Raveendran ◽

...

Keyword(s):

Colorectal Cancer ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Rhesus Macaques ◽

Pedigree Analysis ◽

Hepatic Flexure ◽

Cancer Center ◽

Cancer Syndrome ◽

University Of Texas ◽

Hereditary Nonpolyposis ◽

Md Anderson

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

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Advanced Colon Cancer Before the Age of 20 Years: A Case for Extension of the Current Colonscopy Surveillance Guidelines in Hereditary Nonpolyposis Colorectal Cancer Syndrome

Canadian Journal of Gastroenterology ◽

10.1155/2004/746174 ◽

2004 ◽

Vol 18 (5) ◽

pp. 319-320 ◽

Cited By ~ 1

Author(s):

Victor K Wong ◽

Eric M Yoshida ◽

Anthony G Ryan ◽

Stephen GF Ho ◽

Baljinder Salh

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Pelvic Mass ◽

Cancer Syndrome ◽

Advanced Colon Cancer ◽

Hereditary Nonpolyposis ◽

History Of ◽

Current Guidelines ◽

Colorectal Adenocarcinomas

BACKGROUND:Hereditary nonpolyposis colorectal cancer (HNPCC) currently accounts for between 2% to 6% of all colorectal adenocarcinomas. Controversies exist regarding the current guidelines for colonoscopic screening for colon cancer.CASE REPORT:A case of colon cancer in a young Japanese man with a family history of colon cancer that did not meet the criteria for HNPCC is reported. A malignant pelvic mass discovered shortly before his 20th birthday prompted a colonoscopy. The findings at colonscopy determined that the patient and his family fulfilled the criteria of HNPCC.CONCLUSION:Before finding a pelvic mass metastatic from adenocarcinoma of the ascending colon, this patient was clearly outside of the current guidelines for HNPCC screening. It is suggested that in similar patients, even if they do not fulfill all the criteria for HNPCC, it would be appropriate to consider screening well before the recommended lower age.

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