Abstracts presented at the Spring Conference 2003 of the Cancer Genetics Group, 12–13 May 2003, Southampton, UK


s presented at the Spring Conference 2003 of the Cancer Genetics Group, 12–13 May 2003, Southampton, UK Colorectal cancer genes – what is new? Ian Tomlinson Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK Some of the inherited risk of colorectal cancer can be explained by a tendency to form adenomas. Specific germline mutations in the APC gene cause a multiple adenoma phenotype, but recent data have shown that an almost identical phenotype can result from mutations in the gene MYH which repairs oxidative damage. APC and MYH mutations cause similar phenotypes, but the inheritance and disease mechanisms are very different. The specificity of the MYH-bowel tumour association and comparison with mismatch repair deficiencies are also puzzling. APC and MYH only account for about half of all multiple adenoma cases. Evidence is presented for such an additional gene, HMPS/CRAC1, on 15q which is present as an ancestral mutation in the Ashkenazi population. DNA mismatch repair deficient colon cancer – management options Malcolm Dunlop Colon Cancer Genetics Group, University of Edinburgh and MRC Human Genetics Unit, Edinburgh, UK There are particular management issues when dealing with patients from HNPCC families and in those where there is prior knowledge of development of a tumour deficient in DNA mismatch repair (MMR). Such patients have a current and future risk of metachronous colorectal cancer as well as gynaecological and gastric malignancies. Clinical management strategy should take into account this future cancer risk and should be informed by knowledge about the specific cancer risks. In patients with a known germline MMR gene mutation who develop colorectal cancer, surgery should not only be aimed at radical clearance of the current cancer, but should also be tailored to reduce future cancer risk. Thus prophylactic removal of the majority of the large bowel epithelium should be undertaken by colectomy and ileorectal anastomosis or by proctocolectomy and ileoanal pouch reconstruction in the case of a rectal cancer. Consideration should be given to contemporaneous prophylactic hysterectomy and bilateral oophorectomy for appropriately counselled women past child bearing age who require colorectal resection for cancer. Adjuvant chemotherapy and/or radiotherapy should be offered where indicated, irrespective of DNA mismatch repair gene status, as the evidence is indirect and weak that there is any potential poor outcomes from such therapy. The place of true prophylactic surgery has yet to be fully established, but some women opt for prophylactic pelvic clearance because surveillance measures are of uncertain effectiveness. Prophylactic colectomy may have a place in certain selected patients, but should not be considered routine practice. Surveillance has an important place in managing MMR gene carriers. Two-yearly colonoscopy is mandatory and upper GI endoscopy after the age of 50 years contemporaneously with the colonoscopy is our practice. Two-yearly transvaginal ultrasound and pipelle biopsy is our current surveillance recommendation for female gene carriers who have uterus and ovaries in situ. There is no validated surveillance for small bowel tumours and screening urothelial tumours in such patients has little to recommend it, especially since the risk of such tumours is so low for the individual. With respect to cancer survival, there is a paucity of high quality unselected data on outcome after treatment of primary colorectal cancer. There is data from selected HNPCC families that indicates that survival is good, but these are biased samples. Survival data will be presented from a prospectively recruited cohort of MMR gene carriers which underscores the rationale for surveillance, prophylactic surgery and early detection/treatment of cancer in MMR gene carriers. Hereditary diffuse gastric cancer: characteristics and clinical management Paul D. Pharoah Cancer Research UK, Department of Oncology, University of Cambridge, Cambridge, UK Gastric cancer is the second highest cause of cancer deaths worldwide. There are three main histological subtypes: intestinal, diffuse and mixed. Families with multiple cases of gastric cancer consistent with Mendelian inheritance were first described many years before a molecular basis was first identified. In 1998, a splice-site mutation in CDH1, which encodes the cell cell adhesion molecule E-cadherin, was identified in a 1

DOI: 10.1023/A:1025741009675

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@article{Tomlinson2004AbstractsPA, title={Abstracts presented at the Spring Conference 2003 of the Cancer Genetics Group, 12–13 May 2003, Southampton, UK}, author={Ian Tomlinson}, journal={Familial Cancer}, year={2004}, volume={2}, pages={135-149} }