The Genie Is Out of the Bottle Richard E. Ya Deau MD, FACS, ACHCE - PDF document

The Genie Is Out of the Bottle Richard E. Ya Deau MD, FACS, ACHCE (HON)

23andme Your genetic data “Participatory Research” Richard YaDeau Richard YaDeau Genes vs. Environment 60-80 % Attributable to Genetics  The heritability of AD is estimated to be 60-80%. This means that genetic factors contribute more to individual differences in risk for AD than environmental factors do.  Genetic contributions to AD risk include known factors, such as the APOE gene variants we describe in this report.  Non-genetic risk factors for AD include high blood pressure, high cholesterol, obesity, poorly controlled diabetes, and history of head trauma. Telephone Genetic Counseling Telephone Genetic Counseling Genotypes Predict Weight Loss Success: Genotypes Predict Weight Loss Success: The Right Diet Does Matter The Right Diet Does Matter “Informed” DNA “Informed” DNA www.informeddna.com www.informeddna.com Stanford University School of Medicine Stanford University School of Medicine American Heart Association’s American Heart Association’s Epidemiology and Preventive Medicine Conference Epidemiology and Preventive Medicine Conference Wall Street Journal, March 4 2010 Wall Street Journal, March 4 2010

Stanford study: Stanford study: - Individuals on genotype-appropriate - Individuals on genotype-appropriate diets lost 6.8% /body weight diets lost 6.8% /body weight - Individuals without a diet genotype - Individuals without a diet genotype match lost 1.4% match lost 1.4% - Improvements in clinically related - Improvements in clinically related parameters followed weight loss parameters followed weight loss Interleukin Genetics Interleukin Genetics www.ilgenetics.com www.ilgenetics.com RNA Based Cholesterol Drug Microbial Genomics & Infectious Diseases - 1554 complete bacterial sequences (virtually all - Silence the cholesterol gene pathogens), 4800 now in progress - Interfere with the production of - 2675 viral sequences with the influenza virus cholesterol stimulating proteins showing >40,000 strains - Utilize lipid based delivery systems. - Unique (new) pathogens can be sequenced in < - Results: 50% reduction of cholesterol! 24 hours David A. Relman, M.D. NEJM July 28 2011; 365:347-57 www.alnylam.com 1347-1351 The 50 Million Black Died, Death, ½ of the Yersinia European Pestis Population. Sequenced. Today 2000 Announced deaths per 10/12/2011 year Nature

Ion Torrent’s “Personal Genome Machine” Ion Torrent’s “Personal Genome Machine” “PGM” Total Sequencing all 3 billion DNA units “PGM” Desk-top sequencing - Total sequencing for $1,000 - Identifies viral and bacterial pathogens by their - Results in < 24 Hours. genetics. - Machine capital cost: $149,000 - Sequencer’s initial cost: $450 - Drug companies are using gene variants that - Time to results: 20-30 minutes they can target with drugs. - Already installed in > 500 Physicians’ - BUT who will interpret all of this data? offices and numerous Emergency Rooms. Life Technologies Corp. 1/10/2012 MIT conference on Emerging Technologies (EMTech), October 2011 Jonathan Rothberg @ J.P. Morgan Healthcare Conference Lifetechnologies.com DNA Sequencing to Go Ion PGM™ Sequencer “Oxford Nanopore”: Technology Review 2/17/2012 Size of USB memory stick. Plugs into lap-top. 15 minute run time. $900 Cancer % driven by genetic mutation (s) Genomics and Drug Responses MD Anderson Cancer Center - Cardiovascular drugs Melanoma 73 Thyroid 56 - Infectious diseases Colorectal 51 - Anti-neoplastic drugs Endometrial 41 Lung 41 Pancreatic 41 L. Wang M.D. Mayo Clinic, Breast 41 Genitourinary 29 NEJM March 24 2011; 364:1144-53 Ovarian 21 Head and neck 21 0 10 20 30 40 50 60 70 80

Direct to Consumer Grant me 3 wishes based upon Genome-wide Risk Profiles my genetics: 23andme tests for >1 million common genetic variants #3. That genetic profiles will decrease - 10% sought professional counseling when they the cost and increase the quality of saw their results both my health and my therapeutics. - 26% shared them with their physician - 10% of physicians felt able to use the information from gene testing C. S. Bloss PhD, Scripps Clinic NEJM February 10 2011;364:524-34 Direct to Consumer Genome-wide Risk Profiles The biggest challenge is in data analysis. - No significant increase in anxiety, change in dietary fat intake or exercise programs in Eric Green, director, The National Human Genome Research Institute response to receiving genetic information. www.technologyreview.com, February 10 2011 ! -Results of DTC genetic testing does not affect an individuals health-related behavior. -C. S. Bloss PhD, Scripps Clinic NEJM February 10 2011;364:524-34 “Risk Adopted Therapy” Today hospitals and physicians bring to their patients genetic testing and therapy Consider a vaccine to prevent a specific in a haphazard approach. cancer, e.g. multiple myeloma, by treating patients with the genetic precursors of the There are few institutions that have disease. standardized genetic testing and therapies in order that every appropriate patient would receive them. Kenneth Anderson, Dana-Farber Cancer Institute (OncoPep) www.technologyreview.com May 4 2011

First and foremost we will need data-bases to The FDA has 77 111 approved drugs that are ᴓ support the storage, recall and management of required to have pharmacogenomic information the genetic code for each individual. on their labels. Only 4% of institutions have EMR which can support genetic interpretation and genetic therapy www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm management. Genomics, Health Care and Society NEJM September 15 2011365:1033-41 Genomics, Health Care and Society NEJM September 15 2011365:1033-41 Example: Drug Brand Name Indication (e.g.) The most recent label for warfarin (Coumadin) Abacavir Ziagen HIV-1 includes a table of starting dose on the basis of Azathioprine Imuran Renal Transplant the patients genetics: (CYP2C9 and VKORC1). Carbamazepine Tegretol Epilepsy Cetuximab Erbitux Met. Colon Cancer Does your institution check all patients’ genomic Clopidogrel Plavix Anticoagulation signature before anticoagulant therapy? Irinotecan Camptosar Met. Colon Cancer Panitumumab Vectibix Met. Colon Cancer Trastuzumab Herceptin HER2 Breast Cancer Genomics, Health Care and Society Warfarin Coumadin Anticoagulation NEJM September 15 2011365:1033-41 Genomics, Health Care and Society, NEJM September 15 2011365:1033-41 www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm Frequently asked question about genetics: Genotypes for Richard Ya Deau of the CYP2C9 and VKORC1 genes: 1. What effect will genetic testing have on my SNP Geno- Combination Result health insurance? (genetic discrimination) type rs1799853 CC Two acts (GINA Dec. 2009 & PPACA 2014) rs1057910 AA CYP2C9 *1/*1, Increased warfarin sensitivity. May protect you from health insurers utilizing your VKORC1 -1639/3673 require decreased warfarin dose. genetic data for coverage: rating, increase of AG premiums, denial of enrollment or exclusions for rs9923231 CT preexisting conditions. This legislation does not apply to Life Insurance.

2. Why is genetic testing so expensive when I can get almost all of my genetic markers done by DTC Hospitals, physicians and a world Hospitals, physicians and a world firms for less the $400? of patients need to prepare of patients need to prepare Patents have been awarded for 20 %! of the human themselves, their systems and their themselves, their systems and their genome, including your genetic sequences and for therapeutic practices to function in therapeutic practices to function in methods of testing and analysis. Judge Robert Sweet ruled March 2010 “DNA is not an environment of genetic an environment of genetic markedly different from a product of nature.” diagnostics and therapies. diagnostics and therapies. In the Justice Department’s brief , “BRCA genes and their relationship to breast cancer are the products of evolution not human invention”. Myriad Genetics has appealed this ruling. I believe genetics will be the I believe genetics will be the unifying resource for a vibrant and unifying resource for a vibrant and successful future throughout the successful future throughout the healthcare phenomenon. healthcare phenomenon.