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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial adenomatous polyposis is rare disease, but it is considered as the most important clinical model for studying cancer control and carcinogenesis in general, by its extremely high risk for colorectal cancer as well as for malignancies of diverse organs which is transmitted by autosomal dominant mode. According to Knudson, the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumor cell and same gene may be involved in both familial and non-familial cases of the tumor. The recent studies by Bodmer et al and by Solomon et al which reported on FAP locus in chromosome 5 and on loss of heterozygosity of this locus in the colorectal cancer have made an important break through in proving the Knudson's hypothesis. The epidemiological, clinical and pathological observations on FAP including our studies has been discussed in the view of these recent development of molecular biology.
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PMID:[Recent trends in studies on carcinogenesis in familial adenomatous polyposis]. 282 45

Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although it is usually not familial, there is a rare dominantly inherited susceptibility to colon cancer, familial adenomatous polyposis (FAP; also often previously called familial polyposis coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These are sufficiently likely to give rise to adenocarcinomas to make prophylactic removal of the colon usual in diagnosed FAP individuals. Adenomas may occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. Adenomata have been suggested to be precancerous states for most colorectal tumours. Knudson has suggested that the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumour cells, and that the same gene may be involved in both familial and non-familial cases of a given tumour. Following up a case report of an interstitial deletion of chromosome 5 in a mentally retarded individual with multiple developmental abnormalities and FAP, we have now shown that the FAP gene is on chromosome 5, most probably near bands 5q21-q22.
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PMID:Localization of the gene for familial adenomatous polyposis on chromosome 5. 303 73

Fascinating progress has been made in the past 2 years in our understanding of the genetic alterations associated with colorectal cancer predisposition and development. First, the genotype-phenotype relationship of the cancer susceptibility syndrome associated with familial adenomatous polyposis has been shown to depend on mutation type. Second, hereditary nonpolyposis colorectal cancer syndromes have been recognized as being frequently associated with a defect in the DNA mismatch-repair pathway. A gene on chromosome 2 called hMSH2, which demonstrates homology with the bacterial repair gene MutS, has been shown to be altered in some families with hereditary nonpolyposis colorectal cancer. A defect on chromosome 3 may act by impairing the same pathway. Genotyping of particular loci, termed microsatellite, provides an easy identification of tumors deficient in mismatch repair. Third, the mechanisms by which the inactivation of tumor-suppressor genes such as p53 and APC may contribute to the tumorigenic process have begun to be elucidated. These different discoveries will have important impacts in the prevention and management of colorectal carcinoma, one of the most frequent human cancers.
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PMID:Advances in the genetics and molecular biology of colorectal tumors. 780 42

Common but weakly penetrant mutations of certain genes may confer an increased susceptibility to colorectal cancer and account for a proportion of 'sporadic' cases. We analysed DNA from 111 colorectal cancer cases and 114 controls for a specific candidate sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2. The variant sequence was found in a quarter of individuals, and there was no difference between cancer cases and controls, according to age of development of cancer or presence of family history. It thus appears that this particular sequence variation is a polymorphism rather than a mutation which increases cancer susceptibility.
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PMID:Intron splice acceptor site sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2. 869 31

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with a marked increase in cancer susceptibility, especially cancer of the colorectum. It is one of the most common cancer predisposing syndromes affecting as many as one in 400 individuals in the Western World. Two (mismatch repair) genes (hMSH2 on chromosome 2p and hMLH1 on chromosome 3p) have recently been identified which appear to be involved in the development of cancer in most of the HNPCC families. Colorectal cancer in HNPCC differs from sporadic colorectal cancer by an early age of onset, a proclivity for the proximal colon, and an excess of synchronous and metachronous colorectal cancers. A variety of extracolonic tumors may be encountered in HNPCC, including cancers of the endometrium, stomach, small bowel, urinary tract (renal pelvis and ureter), biliary system and ovary. The diagnosis HNPCC is currently based upon the combined patient and family data. Future identification of HNPCC will be facilitated by the introduction of genetic markers. Identification of HNPCC families is extremely important, because periodic examination may prevent development of disease and death from cancer.
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PMID:What is hereditary nonpolyposis colorectal cancer (HNPCC). 797 95

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.
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PMID:Mutation of a mutL homolog in hereditary colon cancer. 812 40

Hereditary nonpolyposis colorectal cancer (HNPCC) families are frequently missed in the clinical practice setting. The events leading to the diagnosis of a new HNPCC family are described, with particular attention to the importance of a detailed and extended pedigree, and the delivery of pertinent educational and cancer control recommendations to family members. Clinical clues suggestive of HNPCC include young age at colon cancer onset (< 45 yr), proximal colon cancers, multiple colon cancer, and a family history of colonic cancer or certain extracolonic cancers, including endometrium, stomach, small bowel, and urinary tract. Once the diagnosis is established, management of high-risk patients must be based on an awareness of these cardinal features. The recent identification of the cancer susceptibility locus at chromosome 2p15-16 for a subset of HNPCC families and its cloning should lead to a blood test for the carrier state. HNPCC families must nevertheless be identified before high risk family members can enjoy the benefits of progress in molecular biology. This HNPCC family report illustrates some of the important clues necessary for recognizing such families, and the logistics of detailed evaluation.
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PMID:Identification of an HNPCC family. 814 66

The Lynch syndromes account for about 4 to 6 percent of the total colorectal cancer (CRC) burden. Despite more than two decades of documentation in the literature, many physicians fail to recognize the clinical features of these syndromes. The lack of premonitory physical stigmata, coupled with the absence of a biomarker of cancer susceptibility, mandates full reliance on a well-orchestrated family history for diagnosis. These deficiencies impede cancer control. Even if the diagnosis is made, proper surveillance and management measures that are responsive to the Lynch syndromes' natural history may fail to be implemented. We describe CRC occurrences in patients from four extended Lynch syndrome kindreds. Failures in cancer control were attributable to poor patient compliance and/or to limited physician knowledge about the natural history and surveillance recommendations for the Lynch syndromes. Physicians need to more effectively educate their high-risk patients about the significance of genetic risk, the natural history of CRC, and the appropriate surveillance strategies in the Lynch syndromes.
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PMID:Cancer control problems in the Lynch syndromes. 844 29

Hereditary nonpolyposis colorectal cancer (HNPCC) dates to Warthin's description of family G, which he began studying in 1895. Warthin's observations were not fully appreciated until 1966 when two families with an autosomal dominant inheritance pattern of nonpolyposis colorectal cancer (CRC) and endometrial cancer were described. This condition was first termed the "cancer family syndrome" and was later renamed HNPCC. Some have proposed that HNPCC consists of at least two syndromes: Lynch syndrome I, with hereditary predisposition for CRC having early (approximately 44 years) age of onset, a proclivity (70%) for the proximal colon, and an excess of synchronous and metachronous colonic cancers and Lynch syndrome II, featuring a similar colonic phenotype accompanied by a high risk for carcinoma of the endometrium. Transitional cell carcinoma of the ureter and renal pelvis and carcinomas of the stomach, small bowel, ovary, and pancreas also afflict some families. Current estimates indicate that HNPCC may account for as much as 6% of the total CRC burden. There are no known premonitory phenotypic signs or biomarkers of cancer susceptibility in the Lynch syndromes. This report will summarize current knowledge, with emphasis on the manner in which this knowledge can be employed effectively for diagnosis and management of HNPCC.
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PMID:Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. 848 67

High consumption of fruits and vegetables which are abundant in dietary antioxidants has been linked to a reduced incidence of colorectal cancer. A potential mechanism of dietary anticarcinogenesis involves the induction of detoxifying phase II enzymes, including NAD(P)H:quinone reductase (QR) and glutathione-S-transferase (GST). This study therefore examined the ability of the dietary antioxidant vitamins beta-carotene, alpha-tocopherol and ascorbic acid to induce cellular expression of QR and GST activities in human colon cancer cells. Colo205 cells were cultured in the presence or absence of various concentrations (10(-10) to 10(-5) M) of each antioxidative micronutrient, then assessed for cytosolic QR and GST activities and cell growth. beta-Carotene, alpha-tocopherol and ascorbic acid each resulted in dose-dependent increases in QR activity, without adverse effects upon cell proliferation. To investigate whether the ability of beta-carotene to induce QR may be attributable to its conversion to vitamin A and/or to its antioxidant capacity as a carotenoid, retinol, retinoic acid, and lycopene were similarly tested for their capacity for enzyme induction. Although retinol and retinoic acid were both noted to be antiproliferative at higher concentrations (10(-6) to 10(-5) M), both retinoids stimulated QR at physiological concentrations. Lycopene, a carotenoid which is not converted to vitamin A, was devoid of biologic activity. By contrast with the effects upon QR, GST activity was unaffected by treatment with any of the micronutrients tested in this in vitro model. The results support a hypothesis that a high dietary consumption of vitamins A, E and C may confer partial protection against colorectal cancer by the induction of specific detoxifying enzymes. The antioxidant capacity of beta-carotene appears to have less biologic impact vis-a-vis QR induction than its function as a non-toxic reservoir of vitamin A. Measurements of QR activity within the colorectal mucosa may provide an index of cancer susceptibility, and may be an appropriate surrogate endpoint biomarker for colorectal cancer prevention studies involving diet modification or specific relevant micronutrients.
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PMID:Induction of NAD(P)H:quinone reductase by vitamins A, E and C in Colo205 colon cancer cells. 852 7


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