Inherited colon cancers.
Explore the source record for details and available documents.
Adenomatous Polyposis Coli↗
Biomedical subjects
C Harocopos
Publications and source records attributed to C Harocopos.
In a resource-poor country, mutation identification has the potential to reduce the cost of family management for hereditary nonpolyposis colorectal cancer.
PURPOSE: Colonoscopic surveillance of family members at risk of hereditary nonpolyposis colorectal cancer is difficult in a resource-poor country because of its expense. For family members who live in remote areas, poor communication and limited access to sophisticated medical care make surveillance even more difficult. The identification of the mutation causing the disease will simplify surveillance. Our aim was to assess the impact of mutation analysis on the management of a South African family with more than 150 members at risk for hereditary nonpolyposis colorectal cancer. METHODS: We studied a family that met the Amsterdam criteria for hereditary nonpolyposis colorectal cancer. Colorectal cancer affected 27 members in three generations (evidence from histology in 12, barium enema in 1, and family statements in 14 family members). Leukocyte DNA from family members was tested for linkage to candidate loci for colorectal cancer, and DNA from formalin-fixed cancers from six family members was studied for microsatellite instability. DNA from all available family members was then screened for mutations in the hMLH1 gene. The number of individuals at 50 percent risk was calculated by family pedigree and compared with the number who have the mutation. RESULTS: A disease-causing mutation in exon 13 of hMLH1 segregated with the disorder in members of this kindred. Test results of 100 chromosomes from population-matched controls were negative. Sixty family members between the ages of 16 and 50 years are at 50 percent risk for colon cancer by pedigree analysis, but of these, only 26 (43 percent) have the mutation. CONCLUSION: A mutation in the DNA repair gene hMLH1 was found in family members with hereditary nonpolyposis colorectal cancer and in some unaffected relatives previously at 50 percent risk, but not in unrelated subjects. The blood test for the mutation will simplify management, counseling, and surveillance and help to establish prophylactic colectomy.
Chromosome Segregation↗
Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria.
Hereditary non-polyposis colorectal cancer (HNPCC) is a clinical syndrome characterised by an inherited predisposition to early onset colorectal and uterine cancers and an increased incidence of other cancers. It is caused by germline defects in the human mismatch repair genes. Defects in two of the known mismatch repair genes (namely hMSH2 and hMLH1) account for over 90% of mutations found in HNPCC families. In this study we have identified 14 families that fulfilled the clinical criteria for HNPCC and screened the hMSH2 and hMLH1 genes for germline mutations using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. Seven mutations were identified. Of these, there were five frameshifts, one missense mutation and a further novel mutation that involved separate transition and transversion changes in successive amino acid residues. Three of the mutations were in hMSH2 and four in hMLH1. The identification of germ-line mutations in an HNPCC family enables targeted surveillance and the possibility of early curative intervention. SSCP is a simple and effective method for identifying most mutations in the human mismatch repair genes using DNA from fresh, frozen or archival material.
Adaptor Proteins, Signal Transducing↗
Congenital hypertrophy of retinal pigment epithelium in patients with colonic polyps associated with cancer family syndrome.
Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at-risk individuals.
Adenoma↗
Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom.
To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.
Adolescent↗
Proctocolectomy. 3. Pre- and postoperative care.
Explore the source record for details and available documents.
Colonic Diseases↗
Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic.
OBJECTIVE: To introduce and monitor a screening programme for first degree relatives of patients with colorectal cancer based on their calculated lifetime risk. DESIGN: Lifetime risks were calculated for first degree relatives of patients with colorectal cancer and used to offer screening based on estimated risk. SETTING: A family cancer clinic was set up as part of the North East Thames Regional Genetic Service for relatives of patients who had developed colorectal cancer before the age of 45 and members of families in which multiple cancer had occurred. PATIENTS: Self referrals as well as patients referred by general and hospital practitioners. INTERVENTION: Relatives with a lifetime risk of 1 in 10 or greater (high risk group) were offered screening five yearly by colonoscopy, and those whose risk was between 1 in 10 and 1 in 17 were offered yearly screening for faecal occult blood. Women with family histories compatible with Lynch type II cancer family syndrome were offered screening for breast and pelvic tumours. RESULTS: In four years 715 patients were seen. Acceptance of screening was 90% (644 patients). Of 151 patients screened for faecal occult blood, two were found to have polyps. This screening test was unsatisfactory for the high risk group, having a negative predictive value of 78% in 59 patients tested. Regular screening by colonoscopy was offered to 382 high risk patients; 62 patients with polyps and five with colonic cancer were found. One hundred and ten pedigrees were identified with the Lynch type II cancer family syndrome, and four of 35 women screened were found to have breast cancer. Of 14 relatives aged over 65 with a 1 in 2 risk of site specific colonic cancer or Lynch type II cancer family syndrome, seven were found to have polyps, one of whom had carcinoma in situ. CONCLUSIONS: Family history can be used to identify those at risk of colonic cancer and to target appropriate screening. Colonoscopy detected a high number of premalignant colonic polyps, but faecal occult blood testing was unsatisfactory for those at high risk of colorectal cancer.
Adenomatous Polyposis Coli↗
Stoma care. Choosing the right appliance.
Explore the source record for details and available documents.
Colostomy↗
Screening results in a family cancer clinic: five years experience.
We present our experience so far of screening individuals referred to the Cancer family clinic at St. Mark's Hospital from 1986, with the results of the follow-up of these individuals. 651 individuals from 436 families were offered colonoscopic surveillance at five-yearly intervals. The median age at which the examination was performed was 41 years. Families were subdivided according to family history; 15.8% conformed to the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC). The pathological findings were correlated with the type of pedigree; abnormalities were more often found in males than females (30% of colonoscopies in males revealed adenomas, and 17% in females), and adenoma prevalence increased with age. Adenoma prevalence (27% v.s. 21% at all ages, and 38% v.s. 25% in individuals over the age of 35y.), multiple adenomas and the proportion of proximally sited adenomas were all higher in HNPCC families; however, dysplasia and villous or large adenomas were not more common in individuals from HNPCC families. Four of the 7 carcinoma detected were in HNPCC families (3% v.s. 0.6%).
Adenoma↗