hereditary nonpolyposis colorectal neoplasms

Summary

Summary: A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.

Top Publications

  1. Geary J, Sasieni P, Houlston R, Izatt L, Eeles R, Payne S, et al. Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam Cancer. 2008;7:163-72 pubmed
    ..Breast cancer RR was 1.7 overall. The type of mutation (truncating or other type, and site of mutation) showed no obvious correlation with the presence or absence of extra-colonic cancers in families...
  2. Lynch H, Lynch P, Lanspa S, Snyder C, Lynch J, Boland C. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1-18 pubmed publisher
    ..LS explains only 10-25% of familial CRC...
  3. Koornstra J, Mourits M, Sijmons R, Leliveld A, Hollema H, Kleibeuker J. Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol. 2009;10:400-8 pubmed publisher
    ..No data show efficacy of chemopreventive drugs in reducing the risk of extracolonic cancers for patients with Lynch syndrome...
  4. Lancaster J, Powell C, Kauff N, Cass I, Chen L, Lu K, et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol. 2007;107:159-62 pubmed
    ..This commentary provides guidance on identification of patients who may benefit from hereditary cancer risk assessment for Hereditary Breast/Ovarian Cancer and the Lynch/Hereditary Non-Polyposis Colorectal Cancer syndrome...
  5. Hampel H, Frankel W, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26:5783-8 pubmed publisher
  6. Barrow E, Robinson L, Alduaij W, Shenton A, Clancy T, Lalloo F, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009;75:141-9 pubmed publisher
    ..0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic...
  7. Gylling A, Ridanpää M, Vierimaa O, Aittomaki K, Avela K, Kaariainen H, et al. Large genomic rearrangements and germline epimutations in Lynch syndrome. Int J Cancer. 2009;124:2333-40 pubmed publisher
    ..Our findings have important implications in the diagnosis and management of such families...
  8. Schwitalle Y, Kloor M, Eiermann S, Linnebacher M, Kienle P, Knaebel H, et al. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology. 2008;134:988-97 pubmed publisher
    ..However, the role of FSP-specific immune surveillance mechanisms in HNPCC are unknown at present...
  9. Esplen M, Madlensky L, Aronson M, Rothenmund H, Gallinger S, Butler K, et al. Colorectal cancer survivors undergoing genetic testing for hereditary non-polyposis colorectal cancer: motivational factors and psychosocial functioning. Clin Genet. 2007;72:394-401 pubmed
    ..Findings have implications for future research and potential support needs during the genetic counseling and testing process...

More Information

Publications62

  1. Hofstra R, Spurdle A, Eccles D, Foulkes W, de Wind N, Hoogerbrugge N, et al. Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance. Hum Mutat. 2008;29:1292-303 pubmed publisher
  2. Lynch P. New issues in genetic counseling of hereditary colon cancer. Clin Cancer Res. 2007;13:6857s-61s pubmed
    ..Finally, as investigators make progress with the genetics of these rare diseases, one can anticipate a "cooperative group" approach to clinical trials...
  3. Myrhøj T, Andersen M, Bernstein I. Screening for urinary tract cancer with urine cytology in Lynch syndrome and familial colorectal cancer. Fam Cancer. 2008;7:303-7 pubmed publisher
    ..The aim of this study was to evaluate if Urine Cytology (UC) is an appropriate screening procedure for detecting urinary tract neoplasia at an early stage in persons at risk in Hereditary Non-Polyposis Colorectal Cancer families...
  4. Vasen H, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, et al. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe. Fam Cancer. 2010;9:109-15 pubmed publisher
    ..The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment...
  5. Watson P, Vasen H, Mecklin J, Bernstein I, Aarnio M, Jarvinen H, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123:444-449 pubmed publisher
    ..Other cancer types studied occur too infrequently to justify strenuous cancer control interventions...
  6. van Puijenbroek M, Middeldorp A, Tops C, van Eijk R, van der Klift H, Vasen H, et al. Genome-wide copy neutral LOH is infrequent in familial and sporadic microsatellite unstable carcinomas. Fam Cancer. 2008;7:319-30 pubmed publisher
    ..The approach we describe here shows to be an excellent way to study genome-wide cnLOH in archival mismatch repair deficient tumors...
  7. Pal T, Permuth Wey J, Sellers T. A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer. Cancer. 2008;113:733-42 pubmed publisher
    ..The ability to make such distinctions may be of diagnostic, prognostic, and therapeutic utility...
  8. Gylling A, Nieminen T, Abdel Rahman W, Nuorva K, Juhola M, Joensuu E, et al. Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. Carcinogenesis. 2008;29:1351-9 pubmed publisher
    ..Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways...
  9. Sanchez J, Vogel J, Kalady M, Bronner M, Skacel M, Church J. Identifying Lynch syndrome: we are all responsible. Dis Colon Rectum. 2008;51:1750-6 pubmed publisher
    ..This study evaluated the impact of microsatellite instability pathology findings on Lynch syndrome evaluation by clinicians...
  10. Heijink D, Kleibeuker J, Jalving M, Boersma van Ek W, Koornstra J, Wesseling J, et al. Independent induction of caspase-8 and cFLIP expression during colorectal carcinogenesis in sporadic and HNPCC adenomas and carcinomas. Cell Oncol. 2007;29:409-19 pubmed
    ..Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP)...
  11. Alemayehu A, Tomkova K, Zavodna K, Ventusova K, Krivulcik T, Bujalkova M, et al. The role of clinical criteria, genetic and epigenetic alterations in Lynch-syndrome diagnosis. Neoplasma. 2007;54:391-401 pubmed
    ..Variable methylation background in MLH1 promoter does not affect gene silencing and its role in Lynch-syndrome tumorigenesis is insignificant...
  12. Chen L, Yang K, Little S, Cheung M, Caughey A. Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families. Obstet Gynecol. 2007;110:18-25 pubmed
    ..This study models a comparison of management strategies for women who carry a Lynch/HNPCC mutation...
  13. Martinez Bouzas C, Ojembarrena E, Beristain E, Errasti J, Viguera N, Tejada Minguéz M. High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country. Cancer Lett. 2007;255:295-9 pubmed
    ..Furthermore, our results in the Basque Country show higher percentages of rearrangements than previously published by other authors...
  14. Mecklin J, Aarnio M, Läärä E, Kairaluoma M, Pylvänäinen K, Peltomaki P, et al. Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome. Gastroenterology. 2007;133:1093-8 pubmed
    ..This study was designed to assess the cumulative risk for the development of colorectal adenoma or carcinoma in prospective colonoscopic surveillance...
  15. Nilbert M, Wikman F, Hansen T, Krarup H, Orntoft T, Nielsen F, et al. Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population. Fam Cancer. 2009;8:75-83 pubmed publisher
    ..g. in families were diagnostic material is restricted to archival tissue...
  16. Zhang L. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part II. The utility of microsatellite instability testing. J Mol Diagn. 2008;10:301-7 pubmed publisher
    ..MSI has been used and will continue to prevail as the primary screening tool for identifying HNPCC patients...
  17. Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn. 2008;10:293-300 pubmed publisher
  18. Barrow E, Alduaij W, Robinson L, Shenton A, Clancy T, Lalloo F, et al. Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations. Clin Genet. 2008;74:233-42 pubmed publisher
    ..Current colonoscopic screening guidelines are appropriate...
  19. Pino M, Mino Kenudson M, Wildemore B, Ganguly A, Batten J, Sperduti I, et al. Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. J Mol Diagn. 2009;11:238-47 pubmed publisher
  20. Clendenning M, Baze M, Sun S, Walsh K, Liyanarachchi S, Fix D, et al. Origins and prevalence of the American Founder Mutation of MSH2. Cancer Res. 2008;68:2145-53 pubmed publisher
    ..The consequences of this finding would be that the AFM is significantly more frequent in the United States than was previously predicted...
  21. Hes F. Lynch syndrome: still not a familiar picture. World J Surg Oncol. 2008;6:21 pubmed publisher
    ..Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems...
  22. Clendenning M, Senter L, Hampel H, Robinson K, Sun S, Buchanan D, et al. A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome. J Med Genet. 2008;45:340-5 pubmed publisher
    ..This disparity is primarily due to complications in the study of this gene caused by interference from pseudogene sequences...
  23. Ligtenberg M, Kuiper R, Chan T, Goossens M, Hebeda K, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009;41:112-7 pubmed publisher
    ..Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation...
  24. Lu K. Hereditary gynecologic cancers: differential diagnosis, surveillance, management and surgical prophylaxis. Fam Cancer. 2008;7:53-8 pubmed
    ..For those women without cancer who are found to have a hereditary cancer syndrome, effective counseling in the prevention and early detection of cancers is crucial...
  25. Manne S, Chung D, Weinberg D, Vig H, Catts Z, Cabral M, et al. Knowledge and attitudes about microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:2110-7 pubmed
    ..More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test...
  26. Bujalkova M, Zavodna K, Krivulcik T, Ilencikova D, Wolf B, Kovac M, et al. Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumors. Clin Chem. 2008;54:1844-54 pubmed publisher
    ..We developed a simple, low-cost method based on single-nucleotide polymorphism (SNP) genotyping and capillary electrophoresis for the assessment of LOH at 2 MMR loci simultaneously...
  27. Kovacs M, Papp J, Szentirmay Z, Otto S, Olah E. Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome. Hum Mutat. 2009;30:197-203 pubmed publisher
    ..Thus, analysis of the 3' region of the TACSTD1 gene should be included in the routine mutation screening protocols for HNPCC...
  28. Green R, Parfrey P, Woods M, Younghusband H. Prediction of Lynch syndrome in consecutive patients with colorectal cancer. J Natl Cancer Inst. 2009;101:331-40 pubmed publisher
    ..We used data from such patients to test the ability of four models--Leiden, MMRpredict, PREMM(1,2), and MMRpro--to distinguish between those who did and did not carry DNA mismatch repair gene mutations...
  29. Zighelboim I, Powell M, Babb S, Whelan A, Schmidt A, Clendenning M, et al. Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for Lynch syndrome. Fam Cancer. 2009;8:501-4 pubmed publisher
  30. Grindedal E, Møller P, Eeles R, Stormorken A, Bowitz Lothe I, Landrø S, et al. Germ-line mutations in mismatch repair genes associated with prostate cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2460-7 pubmed publisher
    ..This is similar to the high risk associated with BRCA2 mutations. To our knowledge, this study is the first to indicate that the MMR genes may be among the rare genetic variants that confer a high risk of prostate cancer when mutated...
  31. Wijnen J, Brohet R, van Eijk R, Jagmohan Changur S, Middeldorp A, Tops C, et al. Chromosome 8q23.3 and 11q23.1 variants modify colorectal cancer risk in Lynch syndrome. Gastroenterology. 2009;136:131-7 pubmed publisher
    ..To assess whether these influence CRC risk in the Lynch syndrome, we genotyped these variants in a large series of proven mutation carriers...
  32. Baglietto L, Lindor N, Dowty J, White D, Wagner A, Gomez Garcia E, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102:193-201 pubmed publisher
    ..Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain...
  33. Søreide K. Molecular testing for microsatellite instability and DNA mismatch repair defects in hereditary and sporadic colorectal cancers--ready for prime time?. Tumour Biol. 2007;28:290-300 pubmed
    ..The present knowledge and controversies pertaining to molecular testing of MSI and MMR defects in CRC are presented...
  34. Imai K, Yamamoto H. Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis. 2008;29:673-80 pubmed
    ..This review addresses recent advances in the field of microsatellite instability research...
  35. Jenkins M, Hayashi S, O Shea A, Burgart L, Smyrk T, Shimizu D, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology. 2007;133:48-56 pubmed
    ..Our aim was to identify pathology and other features that independently predict high MSI (MSI-H)...
  36. Overbeek L, Ligtenberg M, Willems R, Hermens R, Blokx W, Dubois S, et al. Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting. Am J Surg Pathol. 2008;32:1246-51 pubmed
    ..An indefinite or aberrant staining result has to be followed by molecular microsatellite instability analysis to confirm the presence of a defective DNA MMR system...
  37. Alemayehu A, Sebova K, Fridrichova I. Redundant DNA methylation in colorectal cancers of Lynch-syndrome patients. Genes Chromosomes Cancer. 2008;47:906-14 pubmed publisher
    ..These methylation-profile differences can lead to more effective molecular diagnosis of Lynch syndrome...
  38. Polydorides A, Mukherjee B, Gruber S, McKenna B, Appelman H, Greenson J. Adenoma-infiltrating lymphocytes (AILs) are a potential marker of hereditary nonpolyposis colorectal cancer. Am J Surg Pathol. 2008;32:1661-6 pubmed publisher
    ..Therefore, increased numbers of AILs and decreased numbers of apoptoses in colorectal adenomas are simple and inexpensive markers that raise the possibility of HNPCC...
  39. Julie C, Tresallet C, Brouquet A, Vallot C, Zimmermann U, Mitry E, et al. Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. Am J Gastroenterol. 2008;103:2825-35; quiz 2836 pubmed publisher
    ..These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed...
  40. Scott R. Modifier genes and HNPCC: variable phenotypic expression in HNPCC and the search for modifier genes. Eur J Hum Genet. 2008;16:531-2 pubmed publisher
  41. Boland C, Koi M, Chang D, Carethers J. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer. 2008;7:41-52 pubmed
  42. Tranø G, Wasmuth H, Sjursen W, Hofsli E, Vatten L. Awareness of heredity in colorectal cancer patients is insufficient among clinicians: a Norwegian population-based study. Colorectal Dis. 2009;11:456-61 pubmed publisher
    ..Among consecutive colorectal cancer (CRC) patients, we aimed at identifying all patients with a hereditary predisposition, and to study a possible discrepancy with assessments made by the responsible clinicians...
  43. Johnson P, Gallinger S, McLeod R. Surveillance colonoscopy in individuals at risk for hereditary nonpolyposis colorectal cancer: an evidence-based review. Dis Colon Rectum. 2006;49:80-93; discussion 94-5 pubmed
    ..This study was designed to evaluate the evidence and make recommendations regarding the optimal frequency of surveillance colonoscopy and the age at which to initiate surveillance based on the best available evidence...
  44. Schmeler K, Lynch H, Chen L, Munsell M, Soliman P, Clark M, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354:261-9 pubmed
    ..We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome...
  45. Müller A, Beckmann C, Westphal G, Bocker Edmonston T, Friedrichs N, Dietmaier W, et al. Prevalence of the mismatch-repair-deficient phenotype in colonic adenomas arising in HNPCC patients: results of a 5-year follow-up study. Int J Colorectal Dis. 2006;21:632-41 pubmed
    ..Therefore, screening for MMR deficiency should not be applied routinely in adenomas with the goal to identify HNPCC patients...
  46. Belvederesi L, Bianchi F, Loretelli C, Gagliardini D, Galizia E, Bracci R, et al. Assessing the pathogenicity of MLH1 missense mutations in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with clinical, genetic and functional features. Eur J Hum Genet. 2006;14:853-9 pubmed
  47. Barnetson R, Tenesa A, Farrington S, Nicholl I, Cetnarskyj R, Porteous M, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med. 2006;354:2751-63 pubmed
    ..The identification of mutations in germ-line DNA mismatch-repair genes at the time of diagnosis of colorectal cancer is important in the management of the disease...
  48. Halvarsson B, Lindblom A, Rambech E, Lagerstedt K, Nilbert M. The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer. Fam Cancer. 2006;5:353-8 pubmed
    ..In summary, isolated loss of PMS2 was found in 8% of the MSI-high tumors in our series, including 8/12 previously unexplained MSI-high tumors, in which mutations either in MLH1 or in PMS2 were identified in five cases...
  49. Clendenning M, Hampel H, LaJeunesse J, Lindblom A, Lockman J, Nilbert M, et al. Long-range PCR facilitates the identification of PMS2-specific mutations. Hum Mutat. 2006;27:490-5 pubmed
    ..705+1G>T, c.736_741del6ins11, c.862_863del, c.1688G>T, and c.2007-1G>A. We conclude that PMS2 mutation detection in selected Lynch syndrome and Lynch syndrome-like patients is both feasible and desirable...
  50. Pistorius S, Kruger S, Hohl R, Plaschke J, Distler W, Saeger H, et al. Occult endometrial cancer and decision making for prophylactic hysterectomy in hereditary nonpolyposis colorectal cancer patients. Gynecol Oncol. 2006;102:189-94 pubmed
    ..In addition to the high lifetime risk for colorectal cancer in mutation carriers, there is also a remarkably increased risk for endometrial cancer (EC)...
  51. Maul J, Warner N, Kuwada S, Burt R, Cannon Albright L. Extracolonic cancers associated with hereditary nonpolyposis colorectal cancer in the Utah Population Database. Am J Gastroenterol. 2006;101:1591-6 pubmed
    ..The data describing the extracolonic cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) are variable...
  52. Bermejo J, Eng C, Hemminki K. Cancer characteristics in Swedish families fulfilling criteria for hereditary nonpolyposis colorectal cancer. Gastroenterology. 2005;129:1889-99 pubmed
  53. Jass J. Hereditary Non-Polyposis Colorectal Cancer: the rise and fall of a confusing term. World J Gastroenterol. 2006;12:4943-50 pubmed
    ..The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out...