HNPCC Info

Please Note:  In an effort to update this informational and personal Blog on HNPCC also known as Lynch Syndrome, many of the comments have been updated as posts. Information on Genetic Colon Cancer is changing every day and every day it affects our family in a most profound way. While the name has changed from HNPCC to a more commonly recognized Lynch Syndrome, this is just the tip of the iceberg. Our 30 year old nephew was recently diagnosed with colon cancer and new questions arose in our family.  Especially considering the fact that he is the son of my sister who's genetic testing in 2004 determined that she did not carry the gene mutation for colon cancer known to run in our family. And so, the journey continues as we continue to advocate for Colon Cancer Awareness and Lynch Syndrome and the effect that it has on the family.  More information will continue to be posted on what we are discovering and the current methodologies in screening and ...

2/25/2011   http://www.medscape.com/viewarticle/735522?src=ptalk

July 10, 2009:   Most HNPCC patients were partially adherent to intensive multi-organ screening; however, both adherent and non-adherent pts indicated their intent to initiate or resume screening. Future research will focus on assessing predictors of adherence, as well as identifying strategies to promote adherence, particularly for evidence-based tests such as colonoscopy. Their docs have to be adherent and knowledgeable too! http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=36054  

July 10, 2009: Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is a type of inherited cancer of the digestive tract, particularly the colon (large intestine) and rectum. People with Lynch syndrome have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women with this disorder also have a high risk of cancer of the endometrium (lining of the uterus) and ovaries. Even though the disorder was originally described as not involving noncancerous (benign) growths (polyps) in the colon, people with Lynch syndrome may occasionally have colon polyps. In individuals with this disorder, colon polyps occur at an earlier age than in the general population. Although the polyps do not occur in greater numbers than in the general population, they are more likely to become cancerous.  

copied from the sloan-ketterington hospital page December 26, 2013:   Important Information for Those Who Have Had Colon Cancer Testing prior to November 2004 If you underwent genetic testing for colorectal cancer prior to November 2004, and the results were negative, you may wish to consider undergoing new tests that have become available since then.For genetic testing of the MLH1, MSH2, and APC genes, a test called Southern blot is now available that looks for gene changes in which large portions of a gene may be missing or rearranged. There is a possibility that your previous genetic tests may not have detected such mutations, if they are present.In addition, three genes that predispose to colorectal cancer – PMS2, MSH6, and MUTYH – have been identified in recent years, and new genetic tests are available to test for mutations in these genes.  

Http://www.mlive.com/health/index.ssf/2011/11/tips_for_colon_cancer_preventi.html

Its all in the family..here is a link to what genetic scientists say.... http://www.medscape.com/viewarticle/734249?src=ptalk

I found this on twitter today. Health Tip: Screening Early for Colorectal Cancer Tue, Aug 03, 2010 Explore and compare medications (HealthDay News) -- The general rule is that most people don't need to be screened for colorectal cancer until the age of 50. But for some who meet certain criteria, earlier screening is recommended. The American Academy of Family Physicians suggests you may be a candidate for earlier colorectal cancer screening if: You have a previous history of polyps or colorectal cancer. Other people in your family have had colorectal cancer or polyps. You've had Crohn's disease or ulcerative colitis. You have an inherited colon cancer syndrome. Your diet largely consists of foods that are high in fat and low in fiber. Copyright © 2010 HealthDay. All rights reserved.

December 8, 2009 Report: Cancer death rates fall. More screening would further reduce colorectal cancer deaths – Dr. James Church http://bit.ly/6hCN7u so we need more screeing of colon cancer....because if it is found too late 92% die and are not receptive to chemotherapy.....  

March 15, 2012:   A long-term follow-up study found that only 12 deaths from colorectal cancer occurred in 2,602 patients who had undergone adenomatous polypectomy, compared with an expected 25.4 deaths from the disease in the general population—a 53% reduction. The study findings appeared recently in the New England Journal of Medicine. Although this was a prospective study, the researchers emphasize that its results offer crucial support for continuing recommendations for screening colonoscopies.  

  8/4/2010:   Hello everyone, I am Dr. Muin Khoury, director of the Office of Public Health Genomics at the Centers for Disease Control and Prevention. You may have heard about different tests. You may even have had patients ask you about these tests or share the results with you. So why aren't personal genomic tests ready for primetime? There are 3 key factors that must be considered in the development and evaluation of genetic tests in clinical practice. First, there is the test's analytic validity, which is the test's ability to accurately and reliably measure the thousands of genetic variants on these tests. In many cases, personal genomic tests do meet quality standards for laboratories. The second thing we have to look at is the clinical validity of these tests, which is the ability of the test to detect or predict particular diseases and health conditions. This is the area for which the data are in so much flux right now. Most common diseases, as ...

1/16/2014 Playlist: Lynch Syndrome Educational Support Workshop www.mskcc.org Medical experts from Memorial Sloan-Kettering discuss Lynch syndrome, a genetic disorder that can cause colon and other cancers.

Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demons...

1993: F S Leach et al. Cell 75 (6), 1215-25 (17 Dec 1993) info:pmid/8261515 Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these patients contain alterations in microsatellite sequences (RER+ phenotype). We have used chromosome microdissection to obtain highly polymorphic markers from chromosome 2p16. These and other markers were ordered in a panel of somatic cell hybrids and used to define a 0.8 Mb interval containing the HNPCC locus. Candidate genes were then mapped, and one was found to lie within the 0.8 Mb interval. We identified this candidate by virtue of its homology to mutS mismatch repair genes. cDNA clones were obtained and the sequence used to detect germline mutations, including those producing termination codons, in HNPCC kindreds. Somatic as well as germline mutations of the gene were identified in RER+ tumor cells. This mutS homolog is therefore likely to be...

1994: N Papadopoulos et al. Science 263 (5153), 1625-9 (18 Mar 1994) info:pmid/8128251 Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene. A search of a large database of expressed sequence tags derived from random complementary DNA clones revealed three additional human mismatch repair genes, all related to the bacterial mutL gene. One of these genes (hMLH1) resides on chromosome 3p21, within 1 centimorgan of markers previously linked to cancer susceptibility in HNPCC kindreds. Mutations of hMLH1 that would disrupt the gene product were identified in such kindreds, demonstrating that this gene is responsible for the disease. These results suggest that defects in any of several mismatch repair genes can cause HNPCC.

1996: K W Kinzler and B Vogelstein Cell 87 (2), 159-70 (18 Oct 1996) info:pmid/8861899 A large body of evidence supports the idea that accumulated genetic changes underlie the development of neoplasia. This multistep process is well illustrated by colorectal cancers, which typically develop over decades and appear to require at least seven genetic events for completion. Even so, inheritance of a single altered gene can result in a marked predisposition to colorectal cancer in two distinct syndromes, Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Recent evidence suggests that the genetic defect in FAP affects the rate of tumor initiation by targeting the gatekeeper function of the APC gene. In contrast, the defect in HNPCC largely affects tumor progression by targeting the genome guardian function of DNA mismatch repair. Studies of these syndromes have provided unique insights into both inherited and sporadic forms of human tumors.

2000: H Iino et al. Gut 47 (1), 37-42 (Jul 2000) info:pmid/10861262 BACKGROUND AND AIM: Hereditary non-polyposis colorectal cancer (HNPCC), as its name implies, is associated with few adenomas, and the early evolution of colorectal neoplasia is poorly understood. In this study our aim was to clarify the genetic profiles of benign polyps in subjects with HNPCC using a combined molecular and immunohistochemical approach. METHODS: Thirty adenomas and 17 hyperplastic polyps were obtained from 24 affected HNPCC subjects. DNA was extracted from paraffin embedded tissue by microdissection and analysed for the presence of microsatellite instability (MSI) and mutations in five genes known to be targets in mismatch repair deficiency (TGFbetaRII, IGF2R, BAX, hMSH3, and hMSH6). Serial sections were stained by immunohistochemistry for hMLH1 and hMSH2. RESULTS: Twenty four (80%) of 30 adenomas showed MSI. Of MSI positive adenomas, 66.7% showed MSI at more than 40% of markers (high level of MSI...

1996: H Muta et al. Cancer 77 (2), 265-70 (15 Jan 1996) info:pmid/8625233 info:doi/10.1002/(SICI)1097-0142(19960115)77:2%3C265::AID-CNCR7%3E3.0.CO;2-L BACKGROUND. Microsatellite instability (MI) has been reported in some sporadic colon tumors and in cases of hereditary nonpolyposis colorectal cancer (HNPCC). The criteria for HNPCC have not been fully defined, and clinical criteria are used to identify as many HNPCC patients as possible. To clarify the conformity of these criteria with the identification of eligible HNPCC cases, we analyzed MI in HNPCC patients diagnosed using clinical criteria. METHODS. Genomic DNA was extracted from surgical specimens of 56 colorectal cancers, including 36 from patients diagnosed with HNPCC using the clinical criteria. We analyzed four microsatellite loci using 32P-labeled primers. RESULTS. Among HNPCC patients diagnosed using clinical criteria, patients who were positive for MI accounted for 62% of Group A (a confirmed group) and 35% of Group B...

1995: R Honchel, K C Halling, and S N Thibodeau Seminars in cell biology 6 (1), 45-52 (Feb 1995) info:pmid/7620121 Recent studies have demonstrated novel alterations of microsatellite DNA in tumor tissue. The alterations, termed microsatellite instability or replication error phenotype, have now been observed in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC), the Muir-Torre syndrome (MTS) and in an increasing number of sporadic tumors. These observations, along with the use of genetic linkage analysis, have led to the identification of at least four genetic susceptibility loci for HNPCC, hMSH2, hMLH1, hPMS1 and hPMS2, each of which are involved in DNA mismatch repair. For those tumors demonstrating microsatellite instability, several different phenotypes may exist, the significance of which is currently unknown. Defective DNA mismatch repair may have important implications for the mechanism of tumorigenesis and the clinical behavior of tumors.

1993: P Peltomäki et al. Cancer research 53 (24), 5853-5 (15 Dec 1993) info:pmid/8261393 Microsatellite instability implying multiple replication errors (RER+ phenotype) characterizes a proportion of colorectal carcinomas, particularly those from patients with the hereditary non-polyposis colorectal carcinoma syndrome. We studied the incidence of microsatellite instability in more than 500 sporadic tumors representing 6 different types of cancer. Apart from colorectal carcinoma [see the paper by Lothe et al. (Cancer Res., 53:5849-5852, 1993)] the RER+ phenotype was found in 18% (6 of 33) of gastric carcinomas and 22% (4 of 18) of endometrial carcinomas. In contrast, no evidence of this abnormality was detected in cancers of the lung (N = 85), breast (N = 84), and testis (N = 86). Importantly, the first three cancers, as opposed to the latter three, are characteristic of the hereditary non-polyposis colorectal carcinoma syndrome. These findings suggest that the cancers belonging t...

1996: M Konishi et al. Gastroenterology 111 (2), 307-17 (Aug 1996) info:pmid/8690195 BACKGROUND mp; AIMS: Microsatellite instability (replication error [RER]) is a characteristic of tumors in hereditary nonpolyposis colon cancer (HNPCC), but the mechanism of HNPCC carcinogenesis is not yet understood. To clarify the nature of HNPCC tumors, RER and genetic changes were compared between HNPCC and non-HNPCC tumors. METHODS: RER and genetic changes were analyzed in 21 HNPCC, 389 familial adenomatous polyposis, and 206 sporadic tumors using polymerase chain reaction, single-strand conformation polymorphism, sequencing, and Southern hybridization. RESULTS. in HNPCC, 95% tumors at all stages showed RER positivity (altered loci, 4.3 of 5). In familial adenomatous polyposis and sporadic tumors, RER positivity (1.7 of 5) was 3% in adenoma and intramucosal carcinoma, 13%-24% in invasive carcinoma, and 35% in carcinoma metastasized to liver. Fifty percent of RER-positive HNPCC tumors had bot...

1994: L A Aaltonen et al. Cancer research 54 (7), 1645-8 (01 Apr 1994) info:pmid/8137274 A replication error (RER) phenotype has been documented both in sporadic colorectal tumors and in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+. All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14 (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1) derived from members of HNPCC families. These data suggest the involvement of mismatch repair deficiency in the premalignan...

2006: DNA mismatch repair genes and colorectal cancer. J M Wheeler, W F Bodmer, and N J Mortensen Gut 47 (1), 148-53 (Jul 2000) info:pmid/10861278 Positional cloning and linkage analysis have shown that inactivation of one of the mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, GTBP/hMSH6) is responsible for the microsatellite instability or replication error (RER+) seen in more than 90% of hereditary non-polyposis colorectal cancers (HNPCC) and 15% of sporadic RER+ colorectal cancers. In HNPCC, a germline mutation (usually in hMLH1 or hMSH2) is accompanied by one further event (usually allelic loss) to inactivate a mismatch repair gene. In contrast, somatic mutations in the mismatch repair genes are not frequently found in sporadic RER+ colorectal cancers. Hypermethylation of the hMLH1 promoter region has recently been described, and this epigenetic change is the predominant cause of inactivation of mismatch repair genes in sporadic RER+ colorectal and other cancers. Inacti...

December 8, 2009:   Report: Cancer death rates fall. More screening would further reduce colorectal cancer deaths – Dr. James Church See Report Post so we need more screeing of colon cancer....because if it is found too late 92% die and are not receptive to chemotherapy.....

Post  From November 21, 2009: In Grand Rapids, Michigan they are studying tumor cells in colon cancer. Did you know that colon cancer cells are resistant to chemotherapy? and if colon cancer is not caught early there is a 92 % mortality rate? Hmmmm......   MLive Article on VanAndel Research Institute Study   November 21, 2009 at 1:08 PM