HNPCC Info

Get the Facts: http://genefacts.org Lynch syndrome is a cancer predisposition syndrome caused by inherited mutations in genes responsible for correcting DNA replication errors. Individuals with Lynch syndrome have a greatly increased risk for colorectal, endometrial, and stomach cancers, and a moderately increased risk for other cancers. Key Points 1-3% of colon cancers attributable to Lynch syndrome Dominant inheritance with reduced penetrance (not all patients with mutations will manifest disease) Diagnosis based on clinical and family history, tumor pathology and/or genetic testing Screening and prophylactic surgeries effective in reducing some, but not all cancer risks Mutations in any of several genes can cause the syndrome

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.  

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...

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...

This is the group that was started on Facebook to bring awareness to HNPCC. Feel free to join this group if you are interested in raising the awareness of genetic colon cancer. We will also be investigating ways to raise funds to help those who can't afford the testing required to diagnose colon cancer.

This poem was sent to me by my cousin Hewitt Madigan's girlfriend Hazel. Hewitt wrote this poem for a friend a week after his friend's brother died. Hewitt died in 2006 from pancreatic cancer. His mother, Judy Madigan, died of colon cancer in 1983. His brother Joel had a colonoscopy after we informed him of the genetic connection. Joel had a partial colectomy due to a cancerous polyp in his colon. Hewitt Madigan, 1957 - 2006 make up a day minute by minute tell me who was and who wasn't in it was the morning a long one the afternoon hot were the fields there pretty were you happy or not? make up a week, day by day tell me who came and who went away did it seem to go fast did it seem to go slow was it during the summer or deep in the snow? make up a life time, the minutes, the days remember the laughter in all of its ways make up a lifetime, the months and the years let me always be with you through the laughter and tears. to jeff from hewitt 6/16/78

Somatic mutations in the hMSH2 gene in microsatellite unstable colorectal carcinomas. A L Børresen et al. Human molecular genetics 4 (11), 2065-72 (Nov 1995) 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 ge...

So after the surgery and the drama what kind of surveillance should a HNPCC carrier have? Since they are at risk for other abdominal cancers like liver, pancreatic, uterine, ovaries, kidneys and small bowel. Some tests that can be done are transvaginal ultrasounds, ultrasound of the kidneys, upper GI, small bowel follow through, sigmoidoscopy, endoscopic exam of the upper GI just to name a few. After surgery, it probably should be determined who will do the followup, the surgeon, gastroenterologist or your primary care physician. The decision would likely depend on who is most knowledgeable about risk factors and current best practice. I will describe some of these tests in upcoming days, so that you can find out what those experiences are like.

How is it used? CEA is most useful to monitor treatment of cancer patients. It is used with patients who have had surgery to measure response to therapy and to monitor whether the disease is recurring. A blood test for CEA is often used as a tumor marker . Physicians can use CEA results to determine the stage and extent of disease and the outlook in patients with cancer, especially gastrointestinal (GI) and, in particular, colorectal cancer . CEA is also used as a marker for other forms of cancer. It has been found helpful in monitoring patients with cancer of the rectum, lung, breast, liver, pancreas, stomach, and ovary. Not all cancers produce CEA; therefore, the CEA test is not used for screening the general population. [ Back to top ] When is it ordered? A CEA test is ordered when the patient’s symptoms suggest the possibility of cancer. The CEA level is also tested before treatment in cancer patients, especially patients with GI cancers. CEA levels are monitored during therapy. It...

Lynch Syndrome: HNPCC There are many reasons to wonder about your risk of colorectal or endometrial cancer - your environment, your diet, your family history. As many as 150,000 new cases of colorectal cancer and over 40,000 cases of endometrial cancer are diagnosed each year. While the majority of colorectal and endometrial cancers are sporadic , or not caused by inherited risk factors, research has shown that up to ten percent of these cases are due to inherited cancer syndromes. One of these inherited syndromes is known as hereditary nonpolyposis colorectal cancer ( HNPCC ). Individuals with HNPCC have up to an 80 percent risk of colorectal cancer and up to a 71 percent risk of endometrial cancer by age 70. This is a large risk compared to the general population's risk, which is just two percent for colorectal cancer and 1.5 percent for endometrial cancer. Additionally, people with HNPCC may have more than one type of cancer. These cancers may be diagnosed at the same or at diff...