lamm1

Ingested Arsenic and CancerWhat’s New?: 

Ingested Arsenic and Cancer What’s New? US Senate Committee on the Environment and Public Works January 30, 2004 Steven H. Lamm, MD Michael B. Kruse, PhD

What is Old?: 

What is Old? EPA cancer risk assessment has used the cancer data from SW Taiwan (primarily bladder cancer cases in the Blackfoot-Disease endemic area) to predict the cancer risk from arsenic in drinking water in the USA.

What are Arsenic Health Problems?: 

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.)

SW Taiwan Study Area: 

SW Taiwan Study Area 42 rural villages in coastal region of SW Taiwan* 27 from original four western districts known as Blackfoot Disease (BFD) Endemic Area 15 from two eastern districts not previously studied area Cancer cases from local cancer registry * (Wu et al., 1989)

Studies of Health Effects of Chronic Arsenic Exposure: 

Studies of Health Effects of Chronic Arsenic Exposure Linked to: -drinking water sources. -arsenic in artesian wells. Black-Foot Disease (BFD).-Unique to SW Taiwan

Skin Cancer Rates: 

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

Effects of Arsenic Exposure: 

Effects of Arsenic Exposure Hyperkeratosis of the hands Skin Cancers on hands, arm and chest

Bladder Cancer Risk(Wu et al., 1989): 

Bladder Cancer Risk (Wu et al., 1989)

Village-Specific Data: 

Village-Specific Data

What’s New?: 

What’s New? New studies in peer-reviewed literature find an absence of the risk NRC and EPA predicted for bladder cancer from arsenic exposure in drinking water, the basis for the 10 ug/L standard.

Let’s See What - #1: 

Let’s 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, 2003;158(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)

Let’s See What - #2: 

Let’s 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 Council’s 2001 risk estimate.”

Steinmaus Study: 

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 ug/L.” 181 cases and 328 controls

Steinmaus Exposures: 

Steinmaus Exposures Exposure Measurements 0-19 ug/L 20-79 ug/L 80-120 u/L > 120 ug/L Exposure Averages* < 5 ug/L 5-40 ug/L > 40 ug/L *Assumes two liters per day

Overall Odds Ratios(Steinmaus et al., 2003): 

Overall Odds Ratios (Steinmaus et al., 2003)

Slide16: 

Smokers and Non-Smokers (Steinmaus et al., 2003) (5 year lag, 5-year highest average exposure)

Summary of Steinmaus: 

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.

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

US Counties Groundwater Study (Lamm et al., 2004) County Level US Data Cancer Mortality Rates (NCI/EPA) 1950-79 Groundwater Arsenic Levels (USGS) > 3 ug/L Groundwater Use (State DEP) 100 % County Populations (US Census) 1960

Study Composition: 

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 ug/L Groundwater source counties

Results: US Outcome Data133 US Counties (Lamm et al., 2004): 

Results: US Outcome Data 133 US Counties (Lamm et al., 2004)

Results: US Outcome: 

Results: US Outcome

Results: US Outcome Data: 

Results: US Outcome Data

Observed vs. Predicted: 

Observed vs. Predicted

Arsenic Effects in the West: 

Arsenic Effects in the West

Arsenic Effects in Nebraska: 

Arsenic Effects in Nebraska

Summary of Lamm: 

Summary of Lamm No increase in bladder cancer mortality risk with increase of arsenic level from 3 to 59 ug/L. No special analysis for known bladder cancer risk factors, I.e., smoking and urbanization.

Other US Studies: 

Other US Studies Bates, Smith and Cantor. Case-Control Study of Bladder Cancer and Arsenic in Drinking Water. American Journal of Epidemiology, 1995;141(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, 1999;107(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]

Why the Difference?: 

Why the Difference?

Another Difference: 

Another Difference US study found consistent results for the regression analysis and for the stratified analysis. Taiwan study shows different results for the regression analysis and for the stratified analysis.

The Regression Analysis: 

The Regression Analysis

Same Data, Stratified Analysis: 

Arsenic Concentration at Interval Midpoint (in mg/L) Same Data, Stratified Analysis 0 10 20 30 40 50 0 100 200 300 400 500 600 700 800 Bladder Cancer SMR

Why the Difference?: 

Why the Difference? We propose that the difference is explained by the fact that the study population received water from two aquifers and suggest that the risk is associated with only one of those aquifers. Further, that US waters are more like the other aquifer.

History of SW Taiwan Studies: 

History of SW Taiwan Studies 1950-1990 – Blackfoot Disease (BFD) among villagers who used artesian wells. 1968-1977 Skin cancer and skin disease in BFD-endemic villages and arsenic in artesian wells. [Tseng] EPA Risk Assessment of 1984 1985-1986 Bladder and Lung cancer with arsenic in artesian wells or duration of usage. [C-J Chen] 1989-2000 Bladder and Lung Cancer with arsenic in wells [Wu; Morales] EPA and NAS Risk Assessments of 1999-2001

Arsenic and Artesian Wells: 

Arsenic and Artesian Wells Chen et al. (1985) showed relevance of distinction between artesian and non-artesian water sources. Standardized Mortality Ratios for Cancers by Well Types in Village 0 500 1000 1500 2000 2500 3000 3500 Colon Liver Lung Skin Kidney Bladder Shallow Both Artesian

Taiwan Artesian Well Water: 

Taiwan Artesian Well Water Median Arsenic levels > 350 mg/L Taiwan > (1000 mg/L USA) Humic Substances - High

Artesian Well Water Sources: 

Artesian Well Water Sources Constructed in 1920s. Used until 1960s, when high levels of arsenic known. Arsenic well medians of 10 - 1411 mg/L.

Study Population: 

Study Population The Wu et al., 1989 study population is comprised of the residents of 42 villages. 14 villages dependent upon artesian water wells. 28 villages have alternative water source (surface or shallow aquifer).

Analysis by Water Source: 

Analysis by Water Source

Observed and Predicted: 

Observed and Predicted

Observations: 

Observations SW Taiwan data do not predict the US risk. There are two different exposure groups and two different risk groups in the SW Taiwan data. The US data fit the predictions derived from the risk for the shallow aquifer villages, but not those for the artesian aquifer villages.

Slide41: 

Thank you.