Métodos de investigación en epidemiología ambiental

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Information about Métodos de investigación en epidemiología ambiental

Published on December 14, 2016

Author: Saludentodas

Source: slideshare.net

1. Craig Steinmaus MD University of California Berkeley craigs@berkeley.edu Coquimbo, Chile December 2016

2. ENVIRONMENTAL EPIDEMIOLOGY: METHODS Arsenic: studies in northern Chile •Ecologic studies •Case control studies •Other aspects of study design Current focus and future directions: •Susceptibility: early-life exposure, obesity •Future studies: mechanisms, low doses, transgenerational effects

3. Mining and smelting Cr-Cu arsenate treated woodArsenic pesticides Roxarsone Most rice Arsenic: common sources #1 Natural arsenic in water

4. Few individual water sources, so few measurements needed Why Do Arsenic Studies In Northern Chile? Region II, Chile: “The driest habitable place on earth” Other Areas Worldwide: Most water from small private wells Thousands of water sources, so its hard to assess the everyone’s exposure

5. Region City or Town Population Average Arsenic Concentration (µg/L) Years 1930-57 1958-70 1971-77 1978-79 1980-87 1988-94 1995+ I Arica 168,594 10 10 10 10 10 10 9 Putre 1,799 1 1 1 1 1 1 1 Iquique 196,941 60 60 60 60 60 60 10 Huara 2,365 30 30 30 30 30 30 30 Pica 5,622 10 10 10 10 10 10 10 Pozo Almonte 9,855 40 40 40 40 40 40 40 II Tocopilla 21,827 250 250 636 110 110 40 10 Maria Elena 6,852 250 250 636 110 110 39 39 Calama 125,946 150 150 287 110 110 40 38 San Pedro 4,522 600 600 600 600 600 600 600 Antofagasta 270,184 90 860 110 110 70 40 10 Mejillones 7,660 90 860 110 110 70 37 10 Taltal 10,101 60 60 60 60 60 60 60 Recent migrants 82,312 <10 <10 <10 <10 <10 <10 <10 Population data are based on the most recent Chile census Concentrations of Arsenic in Drinking Water (µg/L) in Northern Chile by Year

6. Highly exposed in utero and early life 40+ YEARS Long term impacts of early-life exposure: Antofagasta Bornhere Cancer?

7. Smith et al., 1998 Am J Epidemiol 147:660-9 ECOLOGIC STUDIES OF CANCER MORTALITY IN REGION II VS. REST OF CHILE

8. ECOLOGIC STUDIES: Criticisms Ecologic bias: no exposure information at the individual level Confounding by… Smoking Occupation Diet Other In and out migration

9. CASE-CONTROL STUDY: METHODS Study design: Case-control study Study area: Regions 1 and 2 in Northern Chile Outcome: Lung (n=302), bladder (n=232), and kidney cancer (n=123) Time frame: All incident cases from 2007-2010 Case ascertainment: All pathology and radiology departments in the Regions Control ascertainment: Chile Electoral Registry (frequency matched on age and sex) Data collection: In home interviews, structured study questionnaire Exposure assessment: Lifetime residential history linked to an arsenic concentration in the public water supply of each city in Chile (90% coverage) Other data: Occupations, smoking, second hand smoke, medical history, diet, blood, sputum, rna-later, nails, urine Funding: NIH/NIEHS (R01 ES014032-01 and P42 ES04705) Ethics approval: UCB, PUC, Region II (Informed consent obtained)

10. 22. ¿En qué lugares ha vivido Ud. A LO MENOS 6 MESES? Período Lugares Fuente de agua potable en ese lugar Comuna Compañía de Agua municipal Embotellada Otra: Desde Hasta Localidad % % % a. 19 _____ 19 _____ b. 19 _____ 19 _____ c. 19 _____ 19 _____ d. 19 _____ 19 _____ Subject: John Doe Year City As (ug/L) % bottled Adjusted Birth 1967 Antofagasta 860 0 860 1968 Antofagasta 860 0 860 1969 Antofagasta 860 0 860 1970 Antofagasta 860 0 860 1971 Antofagasta 860 0 860 1972 Antofagasta 100 0 100 1973 Antofagasta 100 0 100 1974 Arica 8 0 8 1975 Arica 8 0 8 1976 Arica 8 0 8 1977 Arica 8 0 8 1978 Arica 8 0 8 1979 Arica 8 0 8 1980 Arica 8 0 8 1981 Arica 8 0 8 1982 Arica 8 0 8 1983 Arica 8 0 8 1984 Santiago 3 0 3 1985 Santiago 3 0 3 1986 Santiago 3 0 3 1987 Santiago 3 0 3 1988 Santiago 3 0 3 1989 Santiago 3 0 3 1990 Santiago 3 0 3 1991 Santiago 3 0 3 1992 Santiago 3 0 3 1993 Santiago 3 0 3 1994 Santiago 3 0 3 1995 Santiago 3 0 3 1996 Santiago 3 0 3 1997 Santiago 3 0 3 1998 Santiago 3 0 3 1999 Santiago 3 0 3 2000 Santiago 3 0 3 2001 Iquique 60 50 30 2002 Iquique 60 50 30 2003 Iquique 10 0 10 2004 Iquique 10 0 10 2005 Iquique 10 0 10 2006 Iquique 10 0 10 2007 Iquique 10 0 10 2008 Iquique 10 0 10 2009 Iquique 10 0 10 Interview 2010 Iquique 10 0 10 Arsenic water concentrations Residential history

11. UC Berkeley Arsenic Health Effects Research Group UC Berkeley Superfund Research Program US Collaborators Allan Smith Dave Kalman (University of Washington) Lee Moore (NCI) John Balmes (UCSF) Ken Cantor (NCI) Meera Smith Christine Skibola Luoping Zhang Chile PUC, Region II Catterina Ferreccio Guillermo Marshall Yan Yuan Jane Liaw Martyn Smith Johanna Acevedo Sandra Cortes Many others Craig Steinmaus Fenna Sille

12. 38 YEARS LONG LATENCY: Lived in Antofagasta during the high exposure period Lung cancer OR = 4.35 (2.57-7.36) No confounding by age, gender, mining work, SES, smoking, diet Steinmaus et al. Cancer Epidemiol Biomarkers Prev. 2013 22(4):623; Ferreccio et al. Am J Epidemiol. 2013 1;178(5):813-8 Kidney cancer OR = 11.1 (3.60-- 34.2)# Transitional cell Bladder cancer OR = 6.88 (3.84-12.3)

13. Relative risks (RR) of lung cancer in former smokers RR

14. Future Directions: Susceptibility

15. Highly exposed in utero and early life Bornhere 40+ YEARS Long term impacts of early-life exposure: Antofagasta Bornhere Cancer? Highly exposed as adults

16. BLADDER CANCER ODDS RATIOS (OR) Steinmaus., Cancer Epidemiol Biomarkers Prev. 2014 23:1529-38 Cancer odds ratios comparing subjects exposed > 800 ug/L to those exposed ≤110 ug/l by each age of exposure

17. LUNG CANCER ODDS RATIOS (OR)

18. Smith et al. Environ Health Perspect. 2012;120:1527-31 Ecologic Mortality Study of Early life Exposure: SMRs for Antofagasta for subjects born during or just before the high exposure period

19. OBESITYOBESITY ARSENICARSENIC CANCER INFLAMATION TNF-alpha IL-6 CRP Other possible mechanisms: oxidative stress, immune dysfunction, altered lipid metabolism

20. Born BMI age 20 BMI age 40 BMI 10 years preceding interview ¿Cuál es su talla de adulto? _____”_____” Mtro. Cms. ¿Cuál ha sido su peso más frecuente en su vida de adulto? (En el caso de las mujeres no incluir peso durante el embarazo) a. en los últimos 10 años________Kgr. b. a los 20 años _________Kgr. c. a los 40 años (si es > de 590 años) _____Kgr. AGE

21. Odds ratios for arsenic and lung and bladder cancer: People with low BMI (<90th percentile)

22. Odds ratios for arsenic and lung and bladder cancer: People with high BMI only after age 40

23. Odds ratios for arsenic and lung and bladder cancer: People with high BMI only at age 20, not after

24. Odds ratios for arsenic and lung and bladder cancer: People with high BMI at age 20 and after

25. ENVIRONMENTAL EPIDEMIOLOGY MOLECULAR BIOLOGY Disease mechanisms Surveillance Disease screening Early detection Treatment

26. Breast cancer mortality in Region II (Antofagasta) vs. Region V Smith et al., E Biomedicine [In press]

27. Breast cancer mortality in Region II (Antofagasta) vs. Region V

28. Breast cancer mortality in Region II (Antofagasta) vs. Region V

29. Breast cancer mortality in Region II (Antofagasta) vs. Region V

30. Biologic plausibility Arsenic is an effective treatment for promyelocytic leukemia In vitro experiments with cancerous and noncancerous breast cells

31. Environmental exposure F2 germline F1 F2 F3 Adult disease in the offspring (1st generation) Health effect Health effect (transgenerational) FUTURE STUDIES? TRANSGENERATIONAL EFFECTS

32. Epigenetics: Fetal and early-life is a time of major epigenetic (DNA methylation) programming

33. Anway et al., Science 308: 2005

34. Transgenerational impacts in humans: in Antofagasta? 1958-70 High exposure F0 F2 F1 F3 2016 Ages 0-22 years cancer cancer ??? ???

35. Summary Ecologic and case-control studies Who is most susceptible? Obesity and early-life exposure Breast cancer: complimentary epidemiologic and laboratory studies Public Health Relevance Current regulations do not incorporate susceptibility factors Mechanisms: surveillance, prevention, screening, treatment Where To From Here? Epigenetics: current studies with Northwestern University (DNA methylation) and NCI (mRNA) Multi- and transgenerational? Other susceptibility: stress? Exhaled breath study in Antofagasta Superfund: hypertension, diabetes, prostate cancer, stress in Region II Other chemical exposures in northern Chile?

36. Research Team Catterina Ferreccio Allan H Smith Martyn Smith Guillermo Marshall Johanna Acevedo Yan Yuan Sandra Cortes Luoping Zhang Fenna Sille Jane Liaw Viviana Durán John Balmes Susana Cuevas Lee Moore José Garcia Ken Cantor Rodrigo Meza David Kalman Rodrigo Valdés Roxana Parra Gustavo Valdés Vania Villagra Hugo Benitez Francisca González Teresa Barlaro Vania VanderLinde Juan José Aguirre Maria Isabel Vásquez Liliana Pérez Jacqueline Calle NIEHS P42ES04705, R01CA129558, R01ES014032

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