Genetics in The News

Personalized medicine:
Hope or Hype (or Hoax)

Prasit Phowthongkum MD
Division of Medical Genetics and Genomics
Department of Medicine
Chulalongkorn University
Disclosure
• Medical Genetics Consultant: KCMH, RAMA, BIH, BNH, MPK, PMC1,

PYV
• Laboratory Genetics Consultant: GenePro, EC Genomics and Precision
Medicine, Genforch Co Ltd, Grace Science Co Ltd, PrecisionHealth Co
Ltd
• Honorarium: Roche, Astra, Sanofi-Genzymes, Pfizer, Takeda
• The opinion expressed here is solely that of the speaker and does not
represent or reflect the views of any affiliated institutions unless
explicitly stated
Agenda
• Personalized medicine and related terms

• Genetics and genomics technology
• Evidence based genetics/genomics testing for personalized medicine
Personalized medicine and related terms
• Personalized medicine
• Customized medicine
• Tailored medicine
• Individualized medicine
• Precision medicine
• Targeted therapy
• Genomic-guided therapy
• Pharmacogenomics
• Biomarker-driven treatment
• Stratified medicine
Precision
Stratification
Genetics and Genomics Technology
Genotyping
vs
Sequencing
SNP genotyping vs
Sanger Sequencing vs
Second Generation sequencing (Next generation sequencing NGS or Massively Parallel Sequencing MPS)
Omics
medicine
• Genomics
• Transcriptomics
• Proteomics
• Metabolomics
• Phenomics
• Exposomics
• Multi-omics
• Panoramics
Source of sample
• Human
• Germline testing – blood, saliva, normal tissue
• Somatic testing – affected organs, tumor tissue
• Pathogen (Beyond scope of today’s talk)
• Traditional culture methods
• Molecular Methods: Targeted detection, Meta-
genomics
Evidence based Precision Medicine
• Diagnostic
• Genetic diseases (10% of patients) – Monogenic disorders
• Neurology: Huntington Disease, Familial Frontotemporal Dementia, Familial Early Onset
Alzheimer Disease, Wilson disease
• Cancer syndrome: Li-Fraumeni Syndrome, Cowden Syndrome, Neurofibromatosis type
1,2, Multiple endocrine neoplasia type 1, 2, tuberous sclerosis complex, von Hippel
Lindau syndrome, Hereditary Breast Ovarian Cancer syndrome, Lynch syndrome,
Familial adenomatous polyposis, Birt Hog Dube syndrome, etc
• Renal disorders: ADPKD, ADTKD, Alport syndrome, Hereditary Nephrotic syndrome,
Fabry disease
• Connective tissue disorders and aortopathy: vascular Ehler Danlos syndrome, Marfan
syndrome, Loey-Deitz Syndrome, familial thoracic aortic aneurysm and dissection
• Cardiology: Hypertrophic cardiomyopathy, Dilated cardiomyopathy, TTR related
cardiomyopathy, LVNC, ARVC, Long QT syndrome, Brugada Syndrome
• Lipid disorders: Familial Hypercholesterolemia
• Immunology: Primary Immunodeficiency Syndrome, autoinflammatory disorders
• etc
Evidence based Precision Medicine (2)
• Diagnostic
• Non genetic disorders
• Infectious Diseases: beyond today’s talk
• Non-infectious Diseases: rarely required
• eg leukemia
• CML: BCR/ABL
• APML: PML/RARA
• Predictive – presymptomatic-preventative
• Genetic disorders
• Hereditary breast ovarian cancer syndrome
• Lynch syndrome
• Familial Hypercholesterolemia
• Hypertrophic cardiomyopathy
• Of note: proband should be tested first, then familial

cascade can be recommendedd
• Genetic counseling should be provided pre and post test
by genetic health care professionals
• For disorders that has no current treatment,
presymptomatic test benefit must be discussed before
testing
• Predictive – presymptomatic
• DO NOT RECOMMEND ASHG, ACMG, TMGGA, NCCN
• APOE genotyping for Alzheimer disease
• SNP based genotyping to predict cancer risks, osteoporosis, parkinson,
behavior, talents, food consumption, physical activity or sport performance
• Polygenic risk score
• Prospective, randomized clinical trials of PRS incorporated with established genetic
and nongenetic risk factor prediction in breast cancer screening programs are
needed before implementation of a PRS-stratified breast cancer screening program
(ASCO 2023)
• Across four studies involving 55,685 participants, genetic and lifestyle factors were
independently associated with susceptibility to coronary artery disease. Among
participants at high genetic risk, a favorable lifestyle was associated with a nearly
50% lower relative risk of coronary artery disease than was an unfavorable lifestyle.
(Funded by the National Institutes of Health and others (NEJM 2016)
Monoclonal antibody of Amyloid precursor protein
• Therapeutic
• Genetic diseases
• TTR cardiac amyloidosis
• Familial Hereditary – SiRNA, TTR stabilizer, Liver
transplant
• Wild type TTR amyloidosis – TTR stabilizer
• Fabry disease
• ERT
• Some amenable mutations: molecular
chaperone
• HCM
• Mevacamtan – Actin myosin ATPase inhibitor
• Genotype negative: less response
Evidence based precision medicine (6)
• Therapeutic
• Non genetic disease
• Cancer
• Targeted therapies
• Drug side effect
• HLA and Severe Adverse Drug Reaction
• Epilepsy medicine
• Transplant medicine
• Pain medicine
• Antithrombotic medicine
Cancer
targeted
Therapy
HLA and Carbamazepine Fast Fact Check
• HLAB1502: prevalent in Southeast

Asian (Thai 8.5%, Malays 8.3%, Han
Chinese 8.6%, Filiponos 22%), rare in
European descents and East Asian
(Japan, Korea) (<0.1%)
• In Taiwan, Thailand: Odd Ratio of
carbamazepine induced SJS is very
high from 16.5 in Malays to > 1,000 in
Taiwan
• Northern European : HLA3101- CBZ
hypersensitivity – absence reduced
the risk from 5 to 3.8%
การตรวจที่ครอบคลุมด้วยสิ ทธิประโยชน์สุขภาพถ้วนหน้า
• HLAB1502 ตัง้ แต่ปี 2561 รวมยากันชักชนิดอื่นเพื่อหลีกเลี่ยงผลข้างเคียงหลังการตรวจ
• HER2. ตัง้ แต่ปี 2564 รวมยาพุ่งเป้า ในผูป้ ่ วยระยะลุกลามเท่านัน้
• EGFR. ตัง้ แต่ปี 2564 รวมยาพุ่งเป้า ในผูป้ ่ วยระยะลุกลามเท่านัน้
• Philadelphia chromosome สาหรับ ALL ตัง้ แต่ปี 2564 รวมยาพุ่งเป้า
• BRCA1/2. ตัง้ แต่ปี 2566 (ไม่ได้รวมยา Parb Inhibitor ในสิทธิประโยชน์) รวม screening and
prophylactic surgery
• Lynch syndrome ตัง้ แต่ปี 2566 (ไม่ได้รวมยา Check Point Inhibitor Immunotherapy ในสิทธิ
ประโยชน์) รวม screening ?
บทบาทของแพทย์เวชพันธุศาสตร์กบั การแพทย์แม่นยา
• ตรวจวินิจฉัย พยากรณ์โรค ให้การรักษา และป้องกัน โรคพันธุกรรม จากยีนเดี่ยว
• ให้คาแนะนา โอกาสการถ่ายทอด โอกาสการเกิดซา้ ในครอบครัว ในโรคพหุปัจจัย
• ให้คาปรึกษาห้องปฏิบตั ิการทางพันธุศาสตร์ หรือการเลือกการตรวจทางพันธุศาสตร์ และการแปลผลการตรวจทางพันธุศาสตร์
• Training in Thailand:
• 1 year program certification of medical genetics
• 4 months short course in genetic counseling

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Personalized medicine:

Hope or Hype (or Hoax)

• Medical Genetics Consultant: KCMH, RAMA, BIH, BNH, MPK, PMC1,

• Personalized medicine and related terms

• Of note: proband should be tested first, then familial

• HLAB1502: prevalent in Southeast

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