Nonpolyposis Colorectal Cancer
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What is hereditary nonpolyposis colorectal cancer?Hereditary nonpolyposis colorectal cancer, often called HNPCC or Lynch syndrome, is a type of inherited cancer of the digestive tract, particularly the colon (large intestine) and rectum. People with hereditary nonpolyposis colorectal cancer 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 greatly increased risk of endometrial and ovarian cancer. Even though the disorder is described using the term nonpolyposis, people with hereditary nonpolyposis colorectal cancer may have occasional noncancerous growths called colon polyps. These colon polyps occur at an earlier age than do colon polyps in the general population. Although the polyps do not occur in greater numbers than in the general population, they are more prone to become cancerous. How common is hereditary nonpolyposis colorectal cancer?In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. What genes are related to hereditary nonpolyposis colorectal cancer?Variations of the MLH1, MSH2, MSH6, and PMS2 genes increase the risk of developing hereditary nonpolyposis colorectal cancer. All of these genes are involved in the repair of mistakes made when DNA is copied (DNA replication) in preparation for cell division. Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors. How do people inherit hereditary nonpolyposis colorectal cancer?Hereditary nonpolyposis colorectal cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene is sufficient to increase cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.
Source: National Institutes of Health
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Research reports from University of Helsinki, Department of Medical Genetics provide new insights into colon cancer genetics
2007 JUL 30 -- A report, "Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach," is newly published data in Oncogene. According to recent research published in the journal Oncogene, "Mutations in the DNA mismatch repair gene MLH1 are a major cause of hereditary nonpolyposis colorectal cancer (HNPCC). No mutant phenotype is observed before the wild-type (wt) allele is somatically inactivated in target tissue." "We addressed the mechanisms of MLH1 inactivation in 25 colorectal (CRC) and 32 endometrial cancers (ECs) from MLH1 mutation carriers (Mut1, in-frame genomic deletion; Mut2, out-of-frame splice site mutation; Mut3, missense mutation). By a quantitative method, matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF), utilizing four intragenic single nucleotide polymorphisms and mutations, loss of heterozygosity (LOH) was present in 31/57 (54.4%) of tumors. The wt allele displayed LOH more often than the mutant allele (23/57 vs 8/57, p=0.006). For Mut1, LOH was more frequent in CRC than EC (10/11 vs 1/13, p<0.0001), whereas Mut2 and Mut3 displayed opposite LOH pattern. Moreover, although wt LOH predominated in CRC irrespective of the predisposing mutation, LOH often affected the mutant allele in EC from Mut2 and Mut3 carriers (6/19, 31.6%). MLH1 promoter methylation, which reflected a more widespread hypermethylation tendency, occurred in 4/55 (7.3%) of tumors and was inversely associated with LOH," wrote M. Ollikainen and colleagues, University of Helsinki, Department of Medical Genetics. The researchers concluded: "The patterns of somatic events (LOH and promoter methylation) differ depending on the tissue and germline mutation, which may in part explain the differential tumor susceptibility of different organs in HNPCC. MALDI-TOF provides a novel approach for the detection and quantification of LOH." Ollikainen and colleagues published their study in Oncogene (Mechanisms of inactivation of MLH1 in hereditary nonpolyposis colorectal carcinoma: a novel approach. Oncogene, 2007;26(31):4541-9). For additional information, contact M. Ollikainen, University of Helsinki, Dept. of Medical Genetics, Helsinki, Finland. The publisher's contact information for the journal Oncogene is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England. Keywords: Finland, Helsinki, Colon Cancer Genetics, Colon Cancer, Colon Carcinoma, Colorectal, Gastroenterology, Genetics, Oncology, Rectal Cancer, Rectal Carcinoma. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
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