11/29/2017. Genetics and Cancer ERICA L SILVER, MS, LCGC GENETIC COUNSELOR. Genetics 101. Transcription vs Translation
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1 Genetics and Cancer ERICA L SILVER, MS, LCGC GENETIC COUNSELOR Genetics 101 Transcription vs Translation 1
2 Carcinogenesis and Genetics Normal cell First mutation First mutation Second mutation Second mutation Third mutation Third mutation Cancerous Cell Non-Hereditary Cancer Cancerous cell Hereditary Cancer DNA Mutations DNA Mutations 2
3 Cancer Gene Types Proto-oncogenes Promote normal cell growth Mutation convert to oncogene activation, which results in uncontrolled cell division Tumor suppressor gene Restrains cell growth Loss of function results in unregulated growth DNA repair genes Responsible for DNA proofreading Mutations result in accelerated rate of mutation accumulation Mendelian Inheritance Distribution of Cancer Familial 30% Sporadic 60% Hereditary 10% 3
4 Hereditary Cancer Syndromes Features of a Hereditary Cancer Syndrome Testing Techniques Sanger sequencing Large Rearrangement testing Microarray Next-generation DNA sequencing Whole exome/genome sequencing 4
5 Hereditary Breast and Ovarian Cancer Syndrome BRCA1/2: tumor suppressor genes Cancer risks: Breast Ovarian, fallopian tube, primary peritoneal Prostate Male breast cancer Pancreatic Melanoma (BRCA2) Autosomal dominant inheritance Li-Fraumeni Syndrome TP53: tumor suppressor gene Cancer risks: Breast cancer Sarcoma Brain tumors Leukemia Adrenocortical tumors Autosomal dominant 20 30% de novo rate Hereditary Non-Polyposis Colon Cancer Syndrome: Lynch Syndrome MLH1, MSH2, MSH6, PMS2: DNA mismatch repair genes EPCAM: transmembrane glycoprotein Epigenetic inactivation of MSH2 Cancer risks: Colon cancer Uterine Ovarian Small bowel Gastric GU Autosomal dominant 5
6 Hereditary Diffuse Gastric Cancer CDH1: tumor suppressor gene Cancer risks: Diffuse gastric cancer Lobular breast cancer Signet ring colon cancer Autosomal dominant Nevoid Basal Cell Syndrome: Gorlin Syndrome PTCH1: tumor suppressor gene Cancer risks: Basal cell carcinoma Medulloblastoma Physical characteristics: Odontogenic keratocyst Palmar plantar pits Macrocephaly Autosomal dominant 20 30% de novo Management of Hereditary Cancer Syndromes Surveillance Risk-reducing strategies Chemoprevention Risk avoidance Healthy behaviors 6
7 Psychological Consequences Survivor guilt Transmitter guilt Personal identity Family dynamics Incidental findings Legal Issues HIPAA 1996 GINA Genetic information cannot be used a pre-existing condition or to determine eligibility for coverage Does not protect against rate hikes, access to an individuals genetic information, requiring genetic testing as a condition of coverage 2008 Protects against insurers having access to genetic information and using genetic information during medical underwriting Protects employers for accessing an individual s genetic information and using that information to deny employment Does not protect against the use of genetic information as a pre-existing condition when determining coverage and plans for long-term, life, and disability insurance Does not apply to military personnel, VA, or the Indian Health Service Financial Implications Cost Insurance criteria Coverage of surveillance and preventative surgeries Quality assurance of genetic counseling Quality assurance of laboratory testing CLIA-approved 7
8 Consent Purpose Risks, benefits, and limitations as well as possible results and implications Medical management decisions Incidental findings Accuracy and sensitivity Confidentiality and possible discrimination Right to refuse What is the patient s motivation for pursuing testing? Genetics and the Health Care Provider Privacy and confidentiality GC GT Duty to inform patients Cascade testing Questions? 8
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