2018/3/27 Genetic marker Single nucleotide polymorphism (SNP) Complicated disease have genetic predisposition SNP is a variation in a single nucleotide that occurs at a specific position in the DNA. SNPs have no observable impact on the phenoty pe. High penetrance genes It just influence the predisposition Single nucleotide polymorphism (SNP) b Identifiability Smoking and Lung cancer re than 4000 compounds. most of which are carcinogenic substance he probability of lung nitrosamine. et al. Aerosol: carbon monoxide, benzene, acrolein, et al cancer in smokers was Mechanism of tobacco carcinogenesis 10-20% ccumulation of harmful gene The lung cancer mortality 8.4 times 18 times Drinking and Esophageal Cancer Hereditary susceptibility to lung cancer Polymorphism(SNP)in metabolic enzyme gene 2, Risk genotype. ADHB1(G/A)and ALDH2(G/A) CYPA1 activates some chemical substances in tobacco. such 3, Interaction between alcohol use and genetic variation genotype polycyclic aromatic hydrocarbons, to form active Non-risk genetic marker(G)+ non-drinking CST, coding the detoxifying enzyme, helps excrete toxic sk genetic marker(A) non-drinking metabolite by catalyzing it to form combination with glutathione Risk genetic marker (A) drinking 2-2-45times at is hop stant for individuals carrying high-risk alleles to reduce2018/3/27 6 31 Genetic marker Varghese & Easton, 2010  Complicated disease have genetic predisposition  Genetic markers  High penetrance genes  Single nucleotide polymorphism (SNP)  Genetic markers have two basic characteristics  Heredity  Identifiability. Single nucleotide polymorphism (SNP)  SNP is a variation in a single nucleotide that occurs at a specific position in the DNA.  SNPs have no observable impact on the phenotype.  It just influence the predisposition.  Tobacco smoke contains more than 4000 compounds, most of which are carcinogenic substance.  Particles：nicotine, PAHs (Polycyclic Aromatic Hydrocarbons), nitrosamine, et al.  Aerosol：carbon monoxide, benzene, acrolein, et al.  Mechanism of tobacco carcinogenesis  Induce DNA damage——accumulation of harmful gene mutation——induce cancer  Research by Hammond team： Smoking per day： 10-20 cigarettes 20-40 cigarettes The lung cancer mortality (smoker Vs non-smoker) 8.4 times 18 times Smoking and Lung cancer 34 The probability of lung cancer in smokers was 10-20% ?  Polymorphism (SNP) in metabolic enzyme gene  CYPA1 activates some chemical substances in tobacco, such as polycyclic aromatic hydrocarbons, to form active carcinogens.  CST, coding the detoxifying enzyme, helps excrete toxic metabolite by catalyzing it to form combination with glutathione. Hereditary susceptibility to lung cancer 3、Interaction between alcohol use and genetic variation genotype lifestyle ESCC risk  Non-risk genetic marker (G) + non-drinking reference  Non-risk genetic marker (G) + drinking 1.15 times  Risk genetic marker (A) + non-drinking 1~1.4 times  Risk genetic marker (A) + drinking 2.2~4.5 times 1、Risk lifestyle: drinking Drinking and Esophageal Cancer (ESCC) It is important for individuals carrying high-risk alleles to reduce alcohol use. 2、R Nat Genet. 2012 Oct;44(10):1090-7. isk genotype: ADHB1(G/A) and ALDH2(G/A)