Ingested Arsenic and Cancer Whats New

1
Ingested Arsenic and CancerWhats New?

• For the
• New Mexico Rural Water Association
• March 22, 2004
• Steven H. Lamm, MD
• Michael B. Kruse, PhD
• Consultants in Epidemiology Occupational
  Health, Inc. Washington, DC 202/333-2364
  Steve_at_CEOH.com

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What is Old?

• The NRC and EPA cancer risk assessments used the
  cancer data from SW Taiwan (bladder and lung
  cancer cases in the Blackfoot-Disease endemic
  area) to predict the cancer risk from arsenic in
  drinking water in the USA.
• The highest risk was for bladder cancer among
  males Table ES-1.

3
What are Arsenic Health Problems?

• SW Taiwan the most studied area
• Blackfoot Disease
• Skin Cancer and Hyperkeratosis
• Bladder Cancer and Lung Cancer
• Metabolic Syndrome (CV, DM, etc.)

4
Black-Foot Area Diseases

• Black-foot disease was found only in parts of SW
  Taiwan.
• Hyperkeratosis and Skin Cancer seen in other
  environmental areas like Bangladesh.

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Studies of Health Effects of Chronic Arsenic
Exposure
Black-Foot Disease (BFD).-Unique to SW Taiwan
Linked to -drinking water sources. -arsenic in
artesian wells.
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Effects of Arsenic Exposure
Skin Cancers on hands, arm and chest
Hyperkeratosis of the hands
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• Cancer Rates are expected
• to increase linearly with dosage

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Skin Cancer Rates

• Based on data from 37 artesian well dependent
  villages (Tseng et al., 1968)

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Bladder Cancer Risk(Wu et al., 1989)
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The Regression Analysis
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Same Data, Stratified Analysis
50
Bladder Cancer SMR
40
30
20
10
0
0
100
200
300
400
500
600
700
800
Arsenic Concentration at Interval Midpoint (in
mg/L)
12

• What can explain the two different views of the
  dose-response relationship?

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History of SW Taiwan Studies

• Studies from 1950-1986 concerned effects from
  artesian well waters high in arsenic.
• For the first time, in the Wu et al. (1989) paper
  the distinction of artesian wells was eliminated
  and the analysis considered arsenic alone as the
  only exposure variable.

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Arsenic and Artesian Wells
Bladder
Standardized Mortality Ratios for Cancers by Well
Types in Village
Kidney
Skin
Lung
Liver
Artesian
Both
Colon
Shallow
0
500
1000
1500
2000
2500
3000
3500

• Chen et al. (1985) showed relevance of
  distinction between artesian and non-artesian
  water sources.

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Analysis by Water Source
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New Conundrum

• Which prediction line fits the US data?

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Whats New?
Two studies by two separate research groups find

• No increased bladder cancer rate with arsenic
  exposures at ? 50 ?g/L.
• Taiwan-based estimates overpredict US experience.

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Lets See What - 1

• Steinmaus, Yuan, Bates, and Smith.
• Case-Control Study of Bladder Cancer and Drinking
  Water Arsenic in Western United States. American
  Journal of Epidemiology, 2003158(12)1193-1201
• The overall risks were below those predicted
  using data from highly exposed populations in
  Taiwan. (NRC, 1999 Morales, 2000 NRC, 2001,
  Smith, 1992)

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Lets See What - 2

• Lamm, Engel, Kruse, Feinleib, Byrd, Lai, and
  Wilson.
• Arsenic in Drinking Water and Bladder Cancer
  Mortality in the U.S. An Analysis based on 133
  U.S. Counties. Journal of Occupational and
  Environmental Medicine, 2004 46(3) (pending).
• These results provide a direct estimate of
  arsenic-related cancer risk for U.S. residents
  and exclude the National Research Councils
  2001 risk estimate.

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Steinmaus Study

• Case-Control Study of Bladder Cancer in
  California and Nevada 1994-2000
• Includes Hanford, CA and Fallon, NV, the two
  largest populations in the US exposed to drinking
  water arsenic near 100 ?g/L.
• 181 cases and 328 controls

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Overall Odds Ratios(Steinmaus et al., 2003)
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Summary of Steinmaus

• No increased bladder cancer risk with increasing
  exposure to arsenic in drinking water.
• The possible exception is for smokers who ingest
  arsenic at concentrations near 200 ug/day and is
  seen forty years after exposure.

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• The Lamm (2004) 133 US County Study

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US Counties Groundwater Study(Lamm et al., 2004)

• County Level US Data
• Cancer Mortality Rates (NCI/EPA) 1950-79
• Groundwater Arsenic Levels (USGS) gt 3 ?g/L
• Groundwater Use (State DEP) 100
• County Populations (US Census) 1960

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Study Composition

• 133 counties
• 26 states
• 2.5 million people
• 30 years observation
• 75 million person-years of observation
• 4,537 bladder cancer deaths (WM)
• Arsenic levels from 3 to 59 ?g/L
• Groundwater source counties

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Results US Outcome
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Results US Outcome Data
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Observed vs. Predicted
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Summary of Lamm

• No increase in bladder cancer mortality risk with
  increase of arsenic level from 3 to 59 ?g/L.
• No special analysis for known bladder cancer risk
  factors, i.e., smoking and urbanization.

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Observed and Predicted
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Older US Studies

• Bates, Smith and Cantor.
• Case-Control Study of Bladder Cancer and Arsenic
  in Drinking Water. American Journal of
  Epidemiology, 1995141(6)532-530.
• No association of bladder cancer with either
  measure of arsenic exposure.
• Lewis, Southwick, Quellet-Hellstrom, Rench and
  Calderon EPA
• Drinking Water Arsenic in Utah A Cohort
  Mortality Study. Environmental Health
  Perspectives, 1999107(5)359-365.
• No detectable increase in the risk of bladder or
  lung cancers in the study population due to
  arsenic in drinking water, even...up to 166 ug/L
  EPA re-analysis, 2000

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Summary

• Four US studies, each including exposures above
  50 ?g/L, found no increased risk of bladder
  cancer with increased arsenic exposure.
• This is consistent with the same finding in the
  Taiwan shallow aquifer villages and the recent
  Argentina case-control study (Bates et al., 2004).

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Conclusions

• Prior risk analyses that included the artesian
  well village data overpredict bladder cancer
  risks for the US.
• Analyses that include inappropriate data do not
  serve as a reliable basis for establishing US
  standards.

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• Thank you.