Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC‐like families: Problems in diagnosis, surveillance, and management

Abstract

BACKGROUND To the authors' knowledge, hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most commonly occurring hereditary disorder that predisposes to colorectal carcinoma (CRC), accounting for approximately 2–7% of all CRC cases diagnosed in the U.S each year. Its diagnosis is wholly dependent on a meticulously obtained family history of cancer of all anatomic sites, with particular attention to the pattern of cancer distribution within the family. METHODS The objective of the current study was to illustrate various vexing problems that can deter the diagnosis of HNPCC and, ultimately, its management. This was an observational cohort study. Sixteen HNPCC and HNPCC‐like families were selected from a large resource of highly extended HNPCC families. High‐risk patients were selected from these HNPCC families. An ascertainment bias was imposed by the lack of a population‐based data set. Personal interviews and questionnaires were used for data collection. RESULTS There was an array of difficulties highlighted by limitations in compliance, lack of a clinical or molecular basis for an HNPCC diagnosis, ambiguous DNA findings, problems in genetic counseling, failure to meet Amsterdam or Bethesda criteria, small families, lack of medical and pathologic documentation, poor cooperation of family members and/or their physicians, cultural barriers, economic stress, frequent patient fear and anxiety, perception of insurance discrimination, and limited patient and/or physician knowledge regarding hereditary cancer. CONCLUSIONS The diagnosis and management of HNPCC is predicated on physician knowledge of its phenotypic and genotypic heterogeneity, in concert with the multifaceted problems that impact on patient compliance. Cancer 2004;100:53–64. © 2003 American Cancer Society.

Performance of clinical guidelines compared with molecular tumour screening methods in identifying possible Lynch syndrome among colorectal cancer patients: a Norwegian population-based study

“…Approximately 10 -20% of sporadic CRC tumours have been reported to be MSI-H (Imai and Yamamoto, 2008), and the corresponding proportion in our study was 17%. The prevalence of CRCs associated with LS has been 3 -5% in most studies (de la Chapelle, 2004;Lynch et al, 2004;Vasen et al, 2007), and on the basis of molecular tumour tests, we estimated a prevalence of 3.6%. Most studies of unselected CRC patients have analysed MLH1 and MSH2 genes, as these are most commonly mutated in LS (de la Chapelle, 2004;Domingo et al, 2004;Julie et al, 2008).…”

“…It has been suggested that up to 20 -25% of CRC cases are familial, including heredity caused by identified genetic factors and familial clustering of CRC in which the hereditary patterns are complex or unknown (de la Chapelle, 2004). Lynch syndrome (LS) constitutes 3 -5% of all CRCs (Lynch et al, 2004). In individuals with this autosomal dominant predisposition, CRC tends to develop B20 years earlier than sporadic CRC, and the lifetime risk for CRC is 50 -80% (de la Chapelle, 2004;Strate and Syngal, 2005).…”

“…In individuals with this autosomal dominant predisposition, CRC tends to develop B20 years earlier than sporadic CRC, and the lifetime risk for CRC is 50 -80% (de la Chapelle, 2004;Strate and Syngal, 2005). Patients with LS and family members also have an increased risk of other LS-related tumours (Tables 1 and 2) (de la Chapelle, 2004;Lynch et al, 2004).…”

Surgical management of colorectal cancer: A review of the literature

“…Females at 25-35 years of age should undergo annual transvaginal ultrasonography, endometrial aspirations, and have CA-125 levels checked. Oesophagogasrtoduodenoscopy can be utilised in patients to screen for gastric cancer and ultrasound and urine cytology can be utilised to screen for urinary tract malignancy [11]. Surgical management for patients with HNPCC, when elected, includes either a prophylactic total abdominal colectomy with IRA or a segmental colectomy with yearly colonoscopy [12].…”

MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease

“…MLH1 promoter region methylation, leading to silencing of this gene, is an alternative mechanism to mutation underlying MSI-H in sporadic CRC (Toyota et al, 1999). Genetic testing for hereditary predisposition is therefore critical for effective management of suspected HNPCC kindreds (de la Chapelle, 2004;Lynch et al, 2004;Hampel et al, 2005).…”