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2018/3/27 Alcohol-metabolizing pathwa Precision Prediction M乙an (2)Secondary prevention Alcohol Acetic ac Facilitating the stratification of susceptibility that help to guide timing and intensity of screening programs and avoid overscreening Hereditary breast-ovarian cancer syndrome(HBOC) ng program o Mother died from breast cacer at German HNPCC Consortium recommends Screening Program for e She carries the same Brcal Annual screenng (age 25 onwards or begnning no later than 5 years mutation before the lowest age of onset in family o% risk for breast cancer and a ◆ Physical examination ANGELINA so% it to varan ance Abdominal ultrasound At age 37, opted for mastectomy Ful colonoscopy o Raise public awareness for genomic Gastroscopy (age 35 onwards) testing and prevention Gynecological examination including transvaginal ultrasound Endometrial pipelle biopsy (age 35 om Hereditary cancer syndrome oradic cancer related risk sNP iY BrCA1 muratore coloreetal Esophageal 组前! Thyroid eaneer72018/3/27 7 Alcohol Acetaldehyde (Toxic) ADH ALDH H2O+CO2 Fat Acetic aci Alcohol-metabolizing pathway Precision Prediction (1) Primary prevention (2) Secondary prevention  Facilitating the stratification of susceptibility that help to guide timing and intensity of screening programs and avoid overscreening.  Mother died from breast cacer at age 56, with a BRCA1 mutation  She carries the same BRCA1 mutation  80% risk for breast cancer and a 50% risk for ovarian cancer  At age 37, opted for mastectomy  Raise public awareness for genomic testing and prevention Hereditary breast-ovarian cancer syndrome (HBOC) German HNPCC Consortium recommends Screening Program for Lynch Patients:  Annual screening (age 25 onwards or beginning no later than 5 years before the lowest age of onset in family):  Physical examination  Abdominal ultrasound  Full colonoscopy  Gastroscopy (age 35 onwards)  Gynecological examination including transvaginal ultrasound  Endometrial pipelle biopsy (age 35 onwards) Screening program for Lynch Syndrome(HNPCC) Hereditary cancer syndrome Disease Gene Related cancer Risk Hereditary breast-ovarian cancer syndrome (HBOC) BRCA1, BRCA2 Breast cancer BRCA1 mutation: 44-78%; BRCA2 mutation: 33-54% Ovarian cancer BRCA1 mutation: 18-54%; BRCA12 mutation: 4%-18% Lynch Syndrome,/ Hereditary Non-Polyposis Colorectal Cancer (HNPCC) MLH1,MSH2, MSH6,PMS2, ECAP Colorectal cancer, endometrial cancer, gastric cancer, ovarian cancer, Colorectal cancer: 52-82% endometrial cancer: 25-60% gastric cancer: 6-13% ovarian cancer: 4%-12% Familial adenomatous polyposis (FAP) APC Colorectal cancer, Colorectal adenomatous polyposis 100% Hereditary diffuse gastric cancer,(HDGC) CDH1 Gastric cancer Men:67% Women:83% 42 Sporadic cancer related risk SNP Varghese & Easton, 2010 Cancer type Associated SNP Prostate cancer 103 Breast cancer 125 Colorectal cancer 41 Esophageal cancer 27 Lung cancer 18 Bladder cancer 14 Pancreatic cancer 11 Glioma 9 Thyroid cancer 7
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