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

The Genie Is Out of the Bottle Richard E. Ya Deau, MD FACS, FACHCE (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 Microbial Genomics & Infectious Diseases Profiles in Leukemia - 1554 complete bacterial sequences (virtually all - Acquired mutations accumulate progressively. pathogens), 4800 now in progress - Sub-clones acquire new properties. - 2675 viral sequences with the influenza virus - Profiling provides critical diagnostic showing >40,000 strains categorization. - Unique (new) pathogens can be sequenced in < - Survival is be linked to the therapeutic 24 hours choices based upon this categorization. David A. Relman, M.D. NEJM July 28 2011; 365:347-57 Lucy A. Godley, M.D., Ph.D. NEJM 366;12 March 22 2012 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” “PGM” Desk-top sequencing - Identifies viral and bacterial pathogens by their genetics. - Sequencer’s initial cost: $450 - Time to results: 20-30 minutes - Already installed in > 500 Physicians’ Ion PGM™ Sequencer offices and numerous Emergency Rooms. MIT conference on Emerging Technologies (EMTech), October 2011 www.Lifetechnologies.com Ion Torrent’s “Personal Genome Machine” “PGM” Total Sequencing all 3 billion DNA units - Total sequencing for $1,000 - Results in < 24 Hours. - Machine capital cost: $149,000 - Drug companies are using gene variants that they can target with drugs. - BUT who will interpret all of this data? Installed: Yale, Baylor and Broad Institute Cambridge, MA Life Technologies Corp. 1/10/2012 www.lifetechnologies.com Jonathan Rothberg @ J.P. Morgan Healthcare Conference DNA Sequencing to Go Genomics and Drug Responses - Cardiovascular drugs - Infectious diseases - Anti-neoplastic drugs L. Wang M.D. Mayo Clinic, NEJM March 24 2011; 364:1144-53 “Oxford Nanopore” Size of USB memory stick. Plugs: into lap-top. 15 minute run time. $900. Technology Review 2/17/2012 www.nanoporetech.com .

Cancer % driven by genetic mutation (s) MD Anderson Cancer Center Grant me 3 wishes based upon my genetics: Melanoma 73 Thyroid 56 #3. That genetic profiles will decrease Colorectal 51 Endometrial 41 the cost and increase the quality of Lung 41 both my health and my therapeutics. Pancreatic 41 Breast 41 Genitourinary 29 Ovarian 21 Head and neck 21 0 10 20 30 40 50 60 70 80 Direct to Consumer Direct to Consumer Genome-wide Risk Profiles Genome-wide Risk Profiles 23andme tests for >1 million - No significant increase in anxiety, change in common genetic variants dietary fat intake or exercise programs in - 10% sought professional counseling when they response to receiving genetic information. saw their results ! -Results of DTC genetic testing does not - 26% shared them with their physician affect an individuals health-related - 10% of physicians felt able to use the behavior. information from gene testing -C. S. Bloss PhD, Scripps Clinic C. S. Bloss PhD, Scripps Clinic NEJM February 10 2011;364:524-34 NEJM February 10 2011;364:524-34 “Risk Adopted Therapy” The biggest challenge is in data analysis. Consider a vaccine to prevent a specific cancer, e.g. multiple myeloma, by treating Eric Green, director, The National Human Genome Research Institute patients with the genetic precursors of the www.technologyreview.com, February 10 2011 disease. Kenneth Anderson, Dana-Farber Cancer Institute (OncoPep) www.technologyreview.com May 4 2011

Today hospitals and physicians bring to their patients genetic testing and therapy First and foremost we will need data-bases to in a haphazard approach. support the storage, recall and management of the genetic code for each individual. There are few institutions that have Only 4% of institutions have EMR which can standardized genetic testing and therapies support genetic interpretation and genetic therapy in order that every appropriate patient management. would receive them. Genomics, Health Care and Society NEJM September 15 2011365:1033-41 Drug Brand Name Indication (e.g.) The FDA has 77 111 approved drugs that are ᴓ Abacavir Ziagen HIV-1 required to have pharmacogenomic information Azathioprine Imuran Renal Transplant on their labels. Carbamazepine Tegretol Epilepsy Cetuximab Erbitux Met. Colon Cancer www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm Clopidogrel Plavix Anticoagulation 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 Genotypes for Richard Ya Deau of the CYP2C9 Example: and VKORC1 genes: The most recent label for warfarin (Coumadin) includes a table of starting dose on the basis of SNP Geno- Combination Result type the patients genetics: (CYP2C9 and VKORC1). rs1799853 CC Does your institution check all patients’ genomic rs1057910 AA CYP2C9 *1/*1, Increased warfarin sensitivity. May VKORC1 -1639/3673 require decreased warfarin dose. signature before anticoagulant therapy? AG rs9923231 CT Genomics, Health Care and Society NEJM September 15 2011365:1033-41

Frequently asked question about genetics: 2. Why is genetic testing so expensive when I can get almost all of my genetic markers done by DTC 1. What effect will genetic testing have on my firms for less the $400? health insurance? (genetic discrimination) Patents have been awarded for 20 %! of the human Two acts (GINA Dec. 2009 & PPACA 2014) genome, including your genetic sequences and for methods of testing and analysis. But: protect you from health insurers utilizing your Justice Breyer, (Prometheus:10-1150, 3/20/2012) said genetic data for coverage: rating, increase of “Einstein could not patent his celebrated law that premiums, denial of enrollment or exclusions for E = mc²; nor could Newton have patented the law of preexisting conditions. gravity,”. Several similar cases are on hold. A prominent example is Myriad Genetics, BROCA 1 & 2 This legislation does not apply to Life Insurance. Hospitals, physicians and a world Hospitals, physicians and a world I believe genetics will be the I believe genetics will be the of patients need to prepare of patients need to prepare unifying resource for a vibrant and unifying resource for a vibrant and themselves, their systems and their themselves, their systems and their successful future throughout the successful future throughout the therapeutic practices to function in therapeutic practices to function in healthcare phenomenon. healthcare phenomenon. an environment of genetic an environment of genetic diagnostics and therapies. diagnostics and therapies.