Recommendations for the Care of Individuals With an Inherited Predisposition to Lynch Syndrome
01 Jan 2013-
TL;DR: Burke et al. as mentioned in this paper published an article in JAMA that set forth recommendations for care of individuals with an inherited predisposition to hereditary nonpolyposis colorectal cancer (HNPCC).
Abstract: NEARLY 10 YEARS AGO, BURKE et al published an article in JAMA that set forth recommendations for care of individuals with an inherited predisposition to hereditary nonpolyposis colorectal cancer (HNPCC). This syndrome, described as an autosomal dominant disorder, was characterized by predisposition to early onset colorectal cancer and cancers of the endometrium, small intestine, ovary, hepatobiliary system, kidney, and ureter. Discovery of the genes involved in this disorder meant that genetic testing could identify high-risk individuals. In addition, tumor phenotyping, which greatly facilitates identification of gene carriers, has become clinically available and has been recommended for a subset of individuals with colorectal cancer. This systematic review
Citations
More filters
TL;DR: Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
1,167 citations
TL;DR: The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.
Abstract: Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.
1,097 citations
TL;DR: One of every 35 patients with CRC has LS, and each has at least three relatives with LS; all of whom can benefit from increased cancer surveillance, but IHC is more readily available and helps to direct gene testing.
Abstract: Purpose Identifying individuals with Lynch syndrome (LS) is highly beneficial. However, it is unclear whether microsatellite instability (MSI) or immunohistochemistry (IHC) should be used as the screening test and whether screening should target all patients with colorectal cancer (CRC) or those in high-risk subgroups.
789 citations
Baylor College of Medicine1, University of Southampton2, University of Cambridge3, McGill University4, University of Florence5, University of Vermont6, Netherlands Cancer Institute7, Radboud University Nijmegen8, QIMR Berghofer Medical Research Institute9, International Agency for Research on Cancer10
TL;DR: The current state of sequence‐based genetic testing is reviewed, other standardized reporting systems used in oncology are described, and a standardized classification system for application to sequence-based results for cancer predisposition genes is proposed.
Abstract: Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genetic testing may detect changes that are clearly pathogenic, clearly neutral, or variants of unclear clinical significance. Such variants present a considerable challenge to the diagnostic laboratory and the receiving clinician in terms of interpretation and clear presentation of the implications of the result to the patient. There does not appear to be a consistent approach to interpreting and reporting the clinical significance of variants either among genes or among laboratories. The potential for confusion among clinicians and patients is considerable and misinterpretation may lead to inappropriate clinical consequences. In this article we review the current state of sequence-based genetic testing, describe other standardized reporting systems used in oncology, and propose a standardized classification system for application to sequence-based results for cancer predisposition genes. We suggest a system of five classes of variants based on the degree of likelihood of pathogenicity. Each class is associated with specific recommendations for clinical management of at-risk relatives that will depend on the syndrome. We propose that panels of experts on each cancer predisposition syndrome facilitate the classification scheme and designate appropriate surveillance and cancer management guidelines. The international adoption of a standardized reporting system should improve the clinical utility of sequence-based genetic tests to predict cancer risk.
777 citations
TL;DR: Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential, and subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC.
Abstract: More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC.
741 citations
References
More filters
Book•
01 Jan 1981
TL;DR: Evidence that the various common types of cancer are largely avoidable diseases is reviewed, and it is suggested that, apart from cancer of the respiratory tract, the types of cancers that are currently common are not peculiarly modern diseases and are likely to depend chiefly on some long-established factor.
Abstract: My lecture spanned not only the hour allocated for it in the morning, but also the first half of the round table that afternoon, where it acted as an introduction to the round table discussion that followed. The break between the two sessions was determined only by administrative and not by scientific matters, and so in this published account, the two may be read as a unit.
4,211 citations
National Institutes of Health1, Baylor University Medical Center2, University of California, San Francisco3, Ohio State University4, Thomas Jefferson University5, Mayo Clinic6, French Institute of Health and Medical Research7, University of Texas Health Science Center at Houston8, McGill University9, Karolinska Institutet10, Creighton University11, University of Helsinki12, Fred Hutchinson Cancer Research Center13, Harvard University14
TL;DR: This commentary summarizes the Workshop presentations on HNPCC and MSI testing; presents the issues relating to the performance, specificity, and specificity of the Bethesda Guidelines; outlines the revised Bethesda Guidelines for identifying individuals at risk for H NPCC; and recommend criteria for MSI testing.
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to the development of the Bethesda Guidelines for the identification of individuals with HNPCC who should be tested for MSI. To consider revision and improvement of the Bethesda Guidelines, another HNPCC workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In this commentary, we summarize the Workshop presentations on HNPCC and MSI testing; present the issues relating to the performance, sensitivity, and specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines for identifying individuals at risk for HNPCC; and recommend criteria for MSI testing.
2,899 citations
TL;DR: The establishment of a set of selection criteria for families with hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) to provide a basis for uniformity in collaborative studies and a definition of HNPCC was proposed that was aimed at helping clinicians to identify families.
2,416 citations
Memorial Sloan Kettering Cancer Center1, Harvard University2, Indiana University3, University of Minnesota4, University of Utah5, Boston University6, University of California, San Diego7, Kaiser Permanente8, Virginia Commonwealth University9, Eastern Virginia Medical School10, University of Texas Southwestern Medical Center11, Mayo Clinic12
TL;DR: These guidelines differ from those published in 1997 in several ways: the screening interval for double contrast barium enema has been shortened to 5 years, and colonoscopy is the preferred test for the diagnostic investigation of patients with findings on screening and for screening patients with a family history of hereditary nonpolyposis colorectal cancer.
2,196 citations
TL;DR: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) H. Vasen, M. Mecklin, P. Lynch, and H. Meera Khan present a meta-analysis of 125 cases of patients with central giant cell carcinoma of the colon and rectum found to have had atypical EMTs.
Abstract: The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) H. Vasen;J. Mecklin;P. Meera Khan;H. Lynch; Diseases of the Colon & Rectum
2,079 citations