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るるみにばし
4 years ago
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2 Hill

4 In silico (ERα, ERβ, AR, TR, AhR, In vitro (ERα, ERβ, AR, TR, AhR, ) In vivo (ER, AR, TR, AhR, ) Hold - 4 -

5 - 5 -

6 74.Thiophenol 93.Hexabromocyclododecane 88.Bumetrizole UV - 6 -

7 α Helix No Log [ (M)] 5-7 -

8 - 8 - Ligand / Receptor Complex Coated Antigen Secondary Antibody Chromogenesis Ligand Log [Receptor (M)] Log [Receptor (M)] Log [Receptor (M)] Log [Receptor (M)] Receptor Receptor Antibody Antibody Coated Antigen Secondary Antibody Chromogenesis DAX SHP GCNF1 LRH1 SF1 NOR1 NURR1 NGFIB AR PR MR ERRγ ERRβ ERRα ERβ ERα GR EAR2 COUPβ COUPα PNR TLL TR4 TR2 RXRγ RXRβ RXRα HNF4γ HNF4α CAR PXR VDR FXRβ FXR LXRβ LXRα RORγ RORβ RORα Rev-erb β Rev-erb α PPARγ PPARβ PPARα RARβ RARα TRβ TRα DAX SHP GCNF1 LRH1 SF1 NOR1 NURR1 NGFIB AR PR MR ERRγ ERRβ ERRα ERβ ERα GR EAR2 COUPβ COUPα PNR TLL TR4 TR2 RXRγ RXRβ RXRα HNF4γ HNF4α CAR PXR VDR FXRβ FXR LXRβ LXRα RORγ RORβ RORα Rev-erb β Rev-erb α PPARγ PPARβ PPARα RARβ RARα TRβ TRα

9 α β β β α α α β αβ β α α β β

10 in silico (RBA) ERER in vitro ERERARTR ER Cell free ERE SPRHTPS ERER

11 * F1 * * F2 * * * * * * In silico (ERα, ERβ, AR, TR, AhR, In vitro (ERα, ERβ, AR, TR, AhR, ) Hold In vivo (ER, AR, TR, AhR, )

12 (incidence) mortalityprevalence person-years

14 risk (relative risk, RR)(odds ratio, OR)correlation coefficient /100 10,000 10, , , / /20=4 50/50=1 4/1=

15 80/(80+50k)k 20/(20+50k) {80/(80+50k)}/{20/(20+50k)} 80+50k 20+50k 50k (80/50)/(20/50)(80/20)/(50/50) () study design 1) randomized controlled trial 2) (cohort study) 3) retrospective cohort study 4) (case-control study) 5) (nested case-control study) 6) (cross-sectional study) 7) (ecological study) intervention study observational study random allocation supplement placebo

16 cohort O/E observed to expected ratiostandardized mortality ratio, SMRstandardized incidence ratio, SIR O/E observed O/E expected O/E

17 O/E (case) (control) population controlhospital control matching individual matchingfrequency matching

18 PCB PCB PCB

19 chance (bias) (confounding) (causality) alternative explanations

20 causal inference Hill Hill 1964 U.S. Surgeon General's Advisory Committee on Smoking and Health, 1964 Hill, association (causation) 9 (viewpoints) criteria

21 Department of Health and Human Services1980 The Report on Carcinogens Known to be human carcinogen Reasonably anticipated to be human carcinogen sufficient evidence limited evidence International Agency for Cancer Research1972 IARC IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (a) (b) (c) (a)

22 (a) (c) sufficient evidencea probably limited evidence sufficient evidenceb possibly limited evidence less than sufficient evidence inadequate inadequatelimited probably evidence suggesting lack of carcinogenicity The Health Consequence of Smoking: A Report of the Surgeon General Introduction and approach to causal inference

23 associated with a significant increase1969 a likely risk factor1971 (a major risk factor)(1973) (strong associations)(1974) a major, independent risk factor(1980) the most powerful risk factor1983 a cause and the most powerful risk factor1989 A D Hill Hill evidence against competing noncausal explanations (evidence supporting causal ones [explanations]) Hill Hill

24 Hill

25 Hill AB. The environment and disease: association or causation? Proc Roy Soc Med 1965;58: National Academy of Sciences. Veterans and Agent Orange, Update 2002, Executive Summary. Washington DC: National Academy Press, 2003 National Toxicology Program. Report on Carcinogens. Ninth edition. Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, International Agency for Research on Cancer. Some Internally Deposited Radionuclides. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 78. Lyon: International Agency for Research on Cancer, U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health,

こんにちは由美子です

こんにちは由美子です Prevalence (proportion) 1. 1991 23.8 2. 1960 52 85 2477 310 cross sectional study prevalence Time referent: prevalence 1985 40 45 prevalence 0.5 80 85 43 Time referent 1985 time referent Risk and Cumulative