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Arsenic and Arsenic and Nonmelanoma Skin Nonmelanoma Skin Cancer in SlovakiaCancer in Slovakia
Beate PeschBeate Pesch
Environmental Health Environmental Health Research Institute, Research Institute,
GermanyGermany
Part of the EU-funded Part of the EU-funded Project Project
EXPASCANEXPASCAN ‚Exposure to Arsenic ‚Exposure to Arsenic
and Cancer in Central & and Cancer in Central & Eastern Europe‘Eastern Europe‘
www.icconsultants.co.uk/www.icconsultants.co.uk/EXPASCAN.htmlEXPASCAN.html
PARTNERS
Imperial College & IC Consultants, London, UK
State Health Institutes, Prievidza, Bankska Bystrica, SK
Institute of Hygiene and Epidemiology, Prague, CZ
Environmental Health Research Institute, Duesseldorf, D
University of Cluj, RO
ObjectiveObjective
Estimation of the risk of Estimation of the risk of
environmental arsenic environmental arsenic
exposure from power plant exposure from power plant
emissions for non-melanoma emissions for non-melanoma
skin cancer (NMSC)skin cancer (NMSC)
Estimation of the risk Estimation of the risk of environmental of environmental arsenic exposurearsenic exposure
Choose study design(s)Choose study design(s) Assess exposureAssess exposure Estimate riskEstimate risk Discuss confoundersDiscuss confounders
Arsenic and arsenic Arsenic and arsenic compoundscompounds
Environmental Health Environmental Health Criteria (EHC) Criteria (EHC) 2nd edition, 224; 20012nd edition, 224; 2001
WHO, GenevaWHO, Geneva
www.inchem.orgwww.inchem.org
Estimate by Distance to Estimate by Distance to the Power Plantthe Power Plant
Environmental As exposureEnvironmental As exposure NMSC incidenceNMSC incidence
Associate As exposure Associate As exposure with NMSC riskwith NMSC risk
& control for covariates& control for covariates
ENO Power Plant (Slovakia)ENO Power Plant (Slovakia)
Environmental Arsenic Environmental Arsenic ExposureExposure
Historical As exposure Historical As exposure Air pollution modelling Air pollution modelling
(Colvile et al. 2001)(Colvile et al. 2001)
Current As exposureCurrent As exposure Measurement of As in soil, house dustMeasurement of As in soil, house dust
(Keegan et al. 2002)(Keegan et al. 2002)
Arsenic Emissions (tons/year) of the ENO Power Plant, Slovakia
0
100
200
1953 1960 1970 1980 1990 1999
Year
As
t/a
-10000 -6000 -2000 2000 6000 10000
Metres west-east from power plant
-10000
-8000
-6000
-4000
-2000
0
2000
4000
6000
8000
10000
Met
res
sou
th-n
ort
h f
rom
po
wer
pla
nt
1 .0E-0051.8E-0053.1E-0055.6E-0051.0E-0041.8E-0043.1E-0045.6E-0041.0E-0031.8E-0033.1E-0035.6E-0031.0E-0021.8E-0023.1E-002
Arsenic immission profile around theElectrarne Novaky power plant, Slovakia
Metres from power plant
Met
res
from
pow
er p
lant
-10000 0 10000
-10000
10000
0
Arsenic (mg/g) in soil 1999
by distance from the plant
Distance N Median Min Max
< 5 km 40 41 14 134
5-10 km 102 23 9 139
>10km 68 20 10 53
90%10%
75%25%
Median
MaximumMinimum
Distance to the power plant
Urin
ary
arse
nic
(As
III+A
sV
+MM
A+DM
A) [µ
g/l]
1
10
< 5 km 5-10 km > 10 km
Arsenic in soil [µg/g]
Uri
nar
y A
rsen
ic (
AsII
I +A
sV+
MM
A+
DM
A)
[µg
/l]
1
10
10 100
r = 0.21 (p<0.01)
y = 3.025 * x 0.237
n = 159
Cancer Incidence Cancer Incidence AnalysisAnalysis
Prievidza district versus Prievidza district versus SlovakiaSlovakia
Within Prievidza district Within Prievidza district
by distance to the plant by distance to the plant
Comparative Incidence Comparative Incidence Figures (CIF) Figures (CIF)
Prievidza district Prievidza district versusversus
Slovakia 1975-84 Slovakia 1975-84
All malignancies 1.1 All malignancies 1.1
NMSC 1.6NMSC 1.6
Lung cancer 1.0 Lung cancer 1.0
Bladder cancer 0.9 Bladder cancer 0.9
CIF by Distance to the CIF by Distance to the Power PlantPower Plant
cutoff 7.5 km 1977-cutoff 7.5 km 1977-19911991
Basal cell carcinoma 1.6Basal cell carcinoma 1.6Squamous cell ca. 1.6Squamous cell ca. 1.6
Lung cancer 1.0Lung cancer 1.0
Bladder cancer 1.1Bladder cancer 1.1
SIR SIR NMSC (1996-1999)NMSC (1996-1999)by Distance to the by Distance to the
PlantPlant
<5km<5km 5-10 km >10km5-10 km >10km
ReferenceReference
District District 1.21.2 1.11.1 0.80.8
0.9- 1.6 1.0-1.3 0.6-0.90.9- 1.6 1.0-1.3 0.6-0.9
Slovakia Slovakia 1.61.6 1.5 1.0 1.5 1.0
1.2- 2.2 1.3-1.7 0.9-1.31.2- 2.2 1.3-1.7 0.9-1.3
Population-based Population-based Case-Control StudyCase-Control Study
264 NMSC cases (1996-99)264 NMSC cases (1996-99)response rate response rate 80% 80%
286 population controls 286 population controls
response rate 72%response rate 72%
Matching by sex, ageMatching by sex, age
Statistical PowerStatistical Power
= 5% one-sided= 5% one-sided = 20% (power 80%)= 20% (power 80%) controls exposed to As=10%controls exposed to As=10% N cases = 264N cases = 264 N controls = 286N controls = 286 RR to be detected >= 1.9RR to be detected >= 1.9
NMSC Risk EstimationNMSC Risk Estimation
Logistic regressionLogistic regression
conditional on age, gender:conditional on age, gender:Odds Ratio (OR), 95% CIOdds Ratio (OR), 95% CI
Potential confounders: Potential confounders: occupational As exposureoccupational As exposure
smokingsmoking
Occupational As Occupational As exposure exposure (Job-Exposure (Job-Exposure
Matrix)Matrix)
AsExp.
Cas Con OR95% CI
No 159 180 1
Low 83 73 1.30.9-1.9
High 22 33 0.80.4-1.4
Cigarette SmokingCigarette Smoking
Pack-years
Cases Controls OR95% CI
< 1 163 165 1
1- < 10 31 21 1.40.7-2.6
10 -< 20 31 41 0.70.4-1.2
20 + 39 59 0.60.4-1.0
Skin Type & UV Skin Type & UV ExposureExposure
Type Cas264
Con286
OR95% CI
Frequentsunburns 22 14
1.80.9-3.5
Lighteyes 148 137
1.41.0-2.0
Blonde/red hair 29 13
2.61.3-5.2
Manyfreckles 16 8
2.20.9-5.3
Fresh Vegetables & Fresh Vegetables & FruitsFruits
Regularconsump.1/week
Cas264
Con286
OR95% CI
Vegetab. 237 265 0.70.4-1.2
Fruits 239 270 0.60.3-1.1
Exposure Assessment Exposure Assessment and Risk Estimationand Risk Estimationfor Environmental for Environmental
ArsenicArsenic
Dietary habitsDietary habits
Residential historyResidential history
Arsenic ExposureArsenic Exposurefrom Dietary Habitsfrom Dietary Habits
AsNut1 AsNut1 == Σ w(f )* I(f) Σ w(f )* I(f) 25 food items f:25 food items f: w(f) food frequencies w(f) food frequencies I(f) annual As intake I(f) annual As intake
AsNut2 AsNut2 = AsNut1 * s = AsNut1 * s if self-support s= 2, else 1 if self-support s= 2, else 1
Arsenic Exposure Arsenic Exposure with Dietary Habitswith Dietary HabitsAsNut2 Cas Con OR
95% CILow 74 91 1Medium 157 173 1.1
0.8-1.6High 33 22 1.8
1.0-3.4Trend 1.3
1.0-1.7
As ExposureAs Exposurefrom Residential Datafrom Residential Data
AsRes1 = Σ E(t)* AsRes1 = Σ E(t)* w(d(t),t) w(d(t),t)
for all places of residence:for all places of residence:E(t) annual emissionE(t) annual emissionw(d(t),t) immission weightw(d(t),t) immission weight
Correction of spatial Correction of spatial selection bias for selection bias for distance-related distance-related variables AsResvariables AsRes
(1) (1) Random re-sampling of Random re-sampling of controls controls SAS SurveyselectSAS Surveyselect
(2) (2) Bootstrap methodBootstrap method OR, 95% CI OR, 95% CI for R=800 re-sampled groups for R=800 re-sampled groups
Arsenic Exposure Arsenic Exposure with Residential Datawith Residential Data
AsRes1 OR95% CI
Low 1Medium 1.7
1.4-2.1High 1.9
1.4-2.6Trend 1.5
1.3-1.7
Environmental Arsenic Environmental Arsenic Exposure & NMSC RiskExposure & NMSC Risk Elevated NMSC incidence in the Elevated NMSC incidence in the
vicinity of the plant.vicinity of the plant. As exposure from dietary and As exposure from dietary and
residential data are associated residential data are associated with excess risk.with excess risk.
Residual confounding can not Residual confounding can not be excluded.be excluded.