复旦大学上海医学院肿瘤学系1.pptVIP

Map with localization of geographic areas where BRCA1/2 mutation carriers were living Breast Cancer Res Tr. 110: 99-109; 2008 Case Report A 43 years old woman. PE: a 2cm mass in the upper-lateral quadrant of left breast. No mass in the right breast. B-US: a mass in the left breast, and no mass in the right one. Pedigree Mammography R L MRI Familial Adenomatous Polyposis Hundreds to thousands of adenomatous polyps at a young age Cancer occurs at an average age of 39 years Diagnosis -- Flexible sigmoidoscopy Prophylactic colectomy At risk for primary adenomas and carcinomas of the duodenum and rectum as well as desmoid tumors, osteomas, thyroid carcinoma, hepatoblastoma, and other hepatopancreatic tumors Familial Adenomatous Polyposis Familial Adenomatous Polyposis APC MYH--30% of patients with multiple adenomas (15 to 100 adenomas) who test negative for APC mutations APC Familial Adenomatous Polyposis APC gene testing Sigmoidoscopy prophylactic colectomy drugs—— Sulindac celecoxib Surveillance —— extracolonic tumors MYH-Associated Polyposis Recessive syndrome Fewer than 100 adenomas Adenomas and CRC at age older than classical FAP(median CRC age 50y) Duodenal adenomas are uncommon Attenuated polyposis with negtive APC gene mutation Hereditary Nonpolyposis Colon Cancer Clinical Features Genetics Clinical Management Hereditary Nonpolyposis Colon Cancer Diagnosis criteria 1991—— Amsterdam criteria 1999—— Amsterdam II criteria 1996—— Bethesda criteria 2004—— revised Bethesda criteria Hereditary Nonpolyposis Colon Cancer Genes MSH2—— 30% MLH1 —— 30% MSH6 PMS1 PMS2 MLH3 Hereditary Nonpolyposis Colon Cancer Linkage study Association study Genome-wide Association Studies (GWAS) Second generation DNA sequencing Finding Cancer Susceptibility Genes Summary: Etiology of Cancer Extrinsic factors Chemical carcinogens Chemotherapeutic Agents Radiation Metal Fibers and Dust Dietary Virus Intrinsic facors Hereditary factors 复旦大学上海医学院肿瘤学系 Recommended Readings: Ab