Dioxin Case Control Study / Prof. Jean Francois Viel

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

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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/m3.

2000 : our 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.

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Over-incidence

SIR NHL : 1.3 (1.1-1.4)SIR STS : 1.4 (1.1-1.9)

: Besançon, Audeux : MSWI

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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.

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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.

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The municipal solid waste incineratorof 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 / m3,– dust: 315.6 mg / Nm3,– hydrogen chlorine: 803.5 mg / Nm3,– exhaust gases not maintained at temperatures ≥ 850°C for

the legal time (> 2 s).

Population and methods

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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,– at a bloc level,– matched for sex and age (5 age categories),– with a 10-to-1 procedure.

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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.

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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.

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Exposure assessment (1)

First-generation Gaussian-type dispersion model.

Surface topography,

Wind rose,

MSWI characteristics,

Etc.

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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.

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Modeled average ground-level dioxin concentrations

< 0.0001 pg/m3

0.0001 - 0.0002 pg/m3

0.0002 - 0.0004 pg/m3

0.0004 - 0.0016 pg/m3

Dioxin concentrations

Municipal solid waste incineratorDoubs riverCity boundarySoil samples

5 km

N

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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.

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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

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Socio-economic characteristics

Very low Low Intermediate High

Persons with a high school diploma (%) 34 30 27 28

Women in labor force (%) 47 49 48 55

Workers in labor force (%) 17 24 26 23

Unemployed in labor force (%) 13 15 15 13

Single woman as head of household (%) 7 8 11 9

Owner-occupied houses (%) 35 32 29 36

Number of persons per dwelling (mean) 2.2 1.9 2.2 2.2

Single-family houses (%) 35 14 12 30

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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 median age was 66 years.

Address matching was successful for 222 cases.

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Association of NHL with dioxin exposure

Dioxin exposure Cases Controls OR (95% CI)

Very low 42 441 1.0

Low 91 952 1.0 (0.7-1.5)

Intermediate 58 681 0.9 (0.6-1.4)

High 31 146 2.3 (1.4-3.8)

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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

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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.

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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

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We 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…