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Dioxin Case Control Study / Prof. Jean Francois Viel
 

Dioxin Case Control Study / Prof. Jean Francois Viel

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Dioxin Case Control Study / Prof. Jean Francois Viel Dioxin Case Control Study / Prof. Jean Francois Viel Presentation Transcript

  • Dioxin emissions from a municipal solid waste incinerator and risk of non-Hodgkin lymphoma: a case-control study. Pr. Jean-François Viel, Faculty of Medicine, Besançon, France
  • Introduction
    • 1997 : the International Agency for Research on Cancer classifies the 2,3,7,8 TCDD as a human carcinogen.
    • 1998 : the French Ministry of Environment reveals that dioxin concentration in exhaust gas from the MSWI of Besançon is 16.3 ng I-TEQ/m 3 .
    • 2000 : o ur team finds evidence for clusters of non-Hodgkin lymphoma (SIR = 1.3) and soft-tissue sarcoma (SIR = 1.4) in the area that contains the MSWI :
      • Viel JF, Arveux P, Baverel J , Cahn JY. Soft–tissue sarcoma and non-Hodgkin’s lymphoma clusters around a municipal solid waste incinerator with high dioxin emission levels. Am J Epidemiol 2000;152:13-19.
  • Over-incidence SIR NHL : 1 . 3 (1 . 1-1 . 4) SIR ST S : 1 . 4 (1 . 1-1 . 9) : Besançon, Audeux : MSWI
  • Introduction (2)
    • These results suggested an airborne route of dioxin exposure, which is at variance with the common assumption that intake from food accounts for over 90% of the burden of dioxins in the general human population.
    • This assumption may not hold for people living in the vicinity of a solid waste incinerator, however.
    • Possible exposure pathways include :
      • direct exposure (vapor inhalation or dermal absorption),
      • more likely, the consumption of plant products or poultry from contaminated areas .
  • Aim
    • To compare the spatial distributions of cases and population-based controls:
      • at the smallest level of geographic resolution,
      • according to their exposure to dioxins emitted by the MSWI,
      • while accounting for some confounding factors.
  • The municipal solid waste incinerator of Besançon, France
    • Began operation in 1971.
    • Located in an urbanized area.
    • Capacity: 7.2 metric tons/hour.
    • Stack: 40 m high.
    • Processing: 67,000 tons of waste (1998).
    • Emissions (1997):
      • dioxin: 16.3 ng I-TEQ / m 3 ,
      • dust: 315.6 mg / Nm 3 ,
      • hydrogen chlorine: 803.5 mg / Nm 3 ,
      • exhaust gases not maintained at temperatures ≥ 850°C for the legal time (> 2 s).
  • Population and methods
  • Population (1)
    • Study period:
      • January 1, 1980 to December 31, 1995.
    • Study area:
      • City of Besançon (since detailed census data were available only for this area).
    • Selection of cases:
      • non-Hodgkin lymphoma incident cases,
      • living in Besançon at the time of diagnosis,
      • obtained from the local cancer registry.
    • Selection of controls:
      • randomly drawn from the population census database,
      • a t a bloc level ,
      • matched for sex and age (5 age categories),
      • with a 10-to-1 procedure.
  • Population (2)
    • Block:
      • the smallest level of geographic resolution,
      • defined only in densely populated areas,
      • typically a quadrangle bounded by four streets,
      • amounting to 705 blocks in Besançon,
      • averaging 161 inhabitants,
      • only 5 age categories (0-19, 20-39, 40-59, 60-74 and 75+ years) are available to researchers, because of French privacy laws.
  • Population (3)
    • Block group:
      • the 705 blocks of the study area
      • are combined in 52 groups,
      • at this level many socio-economic status
      • measures are available:
        • educational,
        • occupational,
        • household-based indicators,
        • etc.
  • Exposure assessment (1)
    • First-generation Gaussian-type dispersion model.
    • Surface
    • topography,
    • Wind
    • rose,
    • MSWI
    • characteristics,
    • Etc.
  • Exposure assessment (2)
    • It was not possible to assess past exposure because past dioxin emission rates had not been collected.
    • However, dispersion modeling is heavily influenced by factors that are stable over time (mean meteorological conditions, terrain elevations and stack height).
    • Thus, we assumed that contour shapes were reliable estimates of past dioxin exposure profiles, provided relative figures rather than absolute figures were used:
      • the contours were classified as very low, low, intermediate, and high exposure areas.
  • Modeled average ground-level dioxin concentrations < 0.0001 pg/m 3 0.0001 - 0.0002 pg/m 3 0.0002 - 0.0004 pg/m 3 0.0004 - 0.0016 pg/m 3 Dioxin concentrations Municipal solid waste incinerator Doubs river City boundary Soil samples 5 km N
  • Geographical information System
    • The respective contours of these modeled ground-level ground-level air concentrations were digitalized and contoured onto the surface of a map.
    • We used residential address geocoding to pinpoint the location of case residence, and block centroid geocoding to pinpoint the location of control residence.
    • We overlaid a map of case residences onto the digital dioxin concentration map to obtain a field -for risk- classification for each cancer patient.
    • In the same way, we attributed a dioxin concentration category to each of the 705 city blocks and 52 block groups.
  • Data analysis
    • We used conditional logistic regressions to calculate odds ratios and 95% confidence intervals for each level of dioxin exposure estimated from the dispersion model.
    • Multilevel models were run to explain the outcome (case/control status) defined at the individual level, while introducing risk factors at the individual level (dioxin exposure) and the block group level (socio-economic characteristics).
  • Results
  • Socio-economic characteristics 30 12 14 35 Single-family houses (%) 2.2 2.2 1.9 2.2 Number of persons per dwelling (mean) 36 29 32 35 Owner-occupied houses (%) 9 11 8 7 Single woman as head of household (%) 13 15 15 13 Unemployed in labor force (%) 23 26 24 17 Workers in labor force (%) 55 48 49 47 Women in labor force (%) 28 27 30 34 Persons with a high school diploma (%) High Intermediate Low Very low
  • Description of the population
    • During the 16-year study period, 225 NHL cases were diagnosed:
      • age-standardized (world) incidence rate: 14.9 per 100,000,
      • to be compared to 7.8 per 100,000 for France as a whole.
    • The proportion of male was 51 %.
    • The media n age was 66 years.
    • Address matching was successful for 222 cases.
  • Association of NHL with dioxin exposure 2.3 (1.4-3.8) 146 31 High 0.9 (0.6-1.4) 681 58 Intermediate 1.0 (0.7-1.5) 952 91 Low 1.0 441 42 Very low OR (95% CI) Controls Cases Dioxin exposure
  • Hierarchical models
    • Adjustment for a wide range of block group characteristics, introduced in turn in a 2-level hierarchical model, did not alter the results.
    • Inclusion of socio-economic measures resulted in ORs ranging:
      • from 0.9 to 1.0, for the low exposure category,
      • from 0.9 to 1.0, for the intermediate exposure category,
      • from 2.1 to 2.4, for the high exposure category.
  • Discussion
  • Strengths
    • We used a population-based design.
    • This GIS-based case-control study improved upon the conventional case-control design:
      • based on a complete directory of city residents (census data),
      • with a high control/case ratio (10-to-1), yielding fairly precise relative risk estimates.
    • The dioxin exposure was retrospectively assessed from a Gaussian-type dispersion model, independently performed by a sub-contracting company.
    • Sensitivity analyses, based on multi-level modeling, were carried out.
  • Limitations
    • We lacked actual exposure data regarding biota or exposed humans, and the accuracy of the dispersion model had not been assessed before.
    • The lack of information pertaining to residence history and time-activity patterns limited our ability to ascertain the duration of exposure.
    • The scarcity of covariates (only age and gender) could potentially confound the relationship between dioxin exposure from the MSWI and NHL:
      • a further study has validated the geographic-based exposure through dioxin measurements from soil samples,
      • a more detailed case-control study, in which dioxins are measured in blood, is currently under way.
  • Summary
    • W e find an increased risk of non-Hodgkin lymphoma in the highest exposure zone around a municipal solid waste incinerator that emitted high levels of dioxins.
    • This finding, together with the non-Hodgkin lymphoma mortality excess reported by Bertazzi et al . around Seveso, lends support to the hypothesis that airborne dioxin exposure may be a public health concern.
      • Floret N, Mauny F, Challier B, Arveux P, Cahn JY, Viel JF. Dioxin emissions from a solid waste incinerator and risk of non-Hodgkin lymphoma. Epidemiology 2003;14:392-398.
  • Thank you for your attention…