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The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and “J-shaped” linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.
Steven H. Lamm; Isabella J. Boroje; Hamid Ferdosi; Jaeil Ahn. A review of low-dose arsenic risks and human cancers. Toxicology 2021, 456, 152768 .
AMA StyleSteven H. Lamm, Isabella J. Boroje, Hamid Ferdosi, Jaeil Ahn. A review of low-dose arsenic risks and human cancers. Toxicology. 2021; 456 ():152768.
Chicago/Turabian StyleSteven H. Lamm; Isabella J. Boroje; Hamid Ferdosi; Jaeil Ahn. 2021. "A review of low-dose arsenic risks and human cancers." Toxicology 456, no. : 152768.
Small for gestational age (SGA) is a well-known consequence of maternal smoking. Here, we newly examine the magnitude of SGA risk by week of gestational age. Singleton live births (N = 3,032,928) with recorded birth weight, gestational age (22–44 weeks), and maternal tobacco use (Y/N) were categorized as to SGA (Y/N), based on 10th percentile gender-specific weights-for-age. SGA prevalence among tobacco users (19.5%) and non-users (9.1%) yielded a significant SGA prevalence rate ratio of 2.15 (2.13–2.16) and a significant adjusted odds ratio of 2.36 (2.34–2.38). The tobacco non-users’ rate was steadily near 9% across the week 22–44 gestational age range. The tobacco users’ rate was steady until week 33 when it rose monotonically through week 37 to about 20% at week 38 and remained high. This pattern for SGA by gestational week was similar for prevalence rates and adjusted ORs. Tobacco use only through week 33 was not seen to be an SGA risk factor. The magnitude of tobacco use as an SGA risk factor for late third trimester births increased during the period of preterm birth and became fully evident with a two-fold risk for full term infants. We newly report the temporal pattern of tobacco-related SGA by week of gestational age. Tobacco-related SGA was only seen for late third trimester births – increasing during weeks 33–37 with a doubling during weeks 38–44. This pattern, informative for issues of mechanism, highlights the potential benefit of extending tobacco cessation programs through the third trimester of pregnancy.
Steven H. Lamm; Hamid Ferdosi; Isabella J. Boroje; Nana Ama Afari-Dwamena; Lu Qian; Elisabeth Dissen Dash; Ji Li; Rusan Chen; Manning Feinleib. Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome. Preventive Medicine Reports 2020, 18, 101080 .
AMA StyleSteven H. Lamm, Hamid Ferdosi, Isabella J. Boroje, Nana Ama Afari-Dwamena, Lu Qian, Elisabeth Dissen Dash, Ji Li, Rusan Chen, Manning Feinleib. Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome. Preventive Medicine Reports. 2020; 18 ():101080.
Chicago/Turabian StyleSteven H. Lamm; Hamid Ferdosi; Isabella J. Boroje; Nana Ama Afari-Dwamena; Lu Qian; Elisabeth Dissen Dash; Ji Li; Rusan Chen; Manning Feinleib. 2020. "Maternal tobacco use: A third-trimester risk factor for small-for-gestational-age pregnancy outcome." Preventive Medicine Reports 18, no. : 101080.
Background: Although inorganic arsenic in drinking water at high levels (100s–1000s μg/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited. Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were <200 ug/L with median <100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009–2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed. Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above. Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.
Jaeil Ahn; Isabella J. Boroje; Hamid Ferdosi; Zachary J. Kramer; Steven H. Lamm. Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water. International Journal of Environmental Research and Public Health 2020, 17, 960 .
AMA StyleJaeil Ahn, Isabella J. Boroje, Hamid Ferdosi, Zachary J. Kramer, Steven H. Lamm. Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water. International Journal of Environmental Research and Public Health. 2020; 17 (3):960.
Chicago/Turabian StyleJaeil Ahn; Isabella J. Boroje; Hamid Ferdosi; Zachary J. Kramer; Steven H. Lamm. 2020. "Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water." International Journal of Environmental Research and Public Health 17, no. 3: 960.
Isabella J. Boroje; Gideon Koren; Steven H. Lamm. Sea water desalination: A newly discovered cause of iodine deficiency. Birth Defects Research 2018, 110, 971 -972.
AMA StyleIsabella J. Boroje, Gideon Koren, Steven H. Lamm. Sea water desalination: A newly discovered cause of iodine deficiency. Birth Defects Research. 2018; 110 (12):971-972.
Chicago/Turabian StyleIsabella J. Boroje; Gideon Koren; Steven H. Lamm. 2018. "Sea water desalination: A newly discovered cause of iodine deficiency." Birth Defects Research 110, no. 12: 971-972.
While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 μg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of <50 μg/L, the historical limit for both the EPA and WHO. Data sources used included USGS for arsenic exposure, NCI for lung cancer outcome, and CDC and US Census Bureau forcovariates. Poisson log-linear models were conducted for male, female, and total populations using for exposure median county arsenic level, maximum arsenic level ≤50 μg/L, and ≥80% population groundwater dependency. Statistically significant negative associations were found in each of the six models in which the exposure was limited to those who had major exposure (≥80% dependency) to low-levels of arsenic (≤50 μg/L). This is the first large ecological study of lung cancer risk from drinking water arsenic levels that specifically examined the dose-response slope for populations whose exposure was below the historical limit of ≤50 μg/L. The models for each of the three populations (total; male; female) demonstrated an association that is both negative and statistically significant.
Steven H. Lamm; Isabella J. Boroje; Hamid Ferdosi; Jaeil Ahn. Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009–2013)—A Negative Association. International Journal of Environmental Research and Public Health 2018, 15, 1200 .
AMA StyleSteven H. Lamm, Isabella J. Boroje, Hamid Ferdosi, Jaeil Ahn. Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009–2013)—A Negative Association. International Journal of Environmental Research and Public Health. 2018; 15 (6):1200.
Chicago/Turabian StyleSteven H. Lamm; Isabella J. Boroje; Hamid Ferdosi; Jaeil Ahn. 2018. "Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009–2013)—A Negative Association." International Journal of Environmental Research and Public Health 15, no. 6: 1200.
Objectives: To identify risk factors for small-for-gestational age (SGA) for counties in central Appalachian states (Kentucky (KY), Tennessee (TN), Virginia (VA), and West Virginia (WV)) with varied coal mining activities. Material and Methods: Live birth certificate files (1990–2002) were...
Hamid Ferdosi; Steve H. Lamm; Nana Ama Afari-Dwamena; Elisabeth Dissen; Rusan Chen; Ji Li; Manning Feinleib. Small-for-gestational age prevalence risk factors in central Appalachian states with mountain-top mining. International Journal of Occupational Medicine and Environmental Health 2017, 31, 11 -23.
AMA StyleHamid Ferdosi, Steve H. Lamm, Nana Ama Afari-Dwamena, Elisabeth Dissen, Rusan Chen, Ji Li, Manning Feinleib. Small-for-gestational age prevalence risk factors in central Appalachian states with mountain-top mining. International Journal of Occupational Medicine and Environmental Health. 2017; 31 (1):11-23.
Chicago/Turabian StyleHamid Ferdosi; Steve H. Lamm; Nana Ama Afari-Dwamena; Elisabeth Dissen; Rusan Chen; Ji Li; Manning Feinleib. 2017. "Small-for-gestational age prevalence risk factors in central Appalachian states with mountain-top mining." International Journal of Occupational Medicine and Environmental Health 31, no. 1: 11-23.
High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1–1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100–150 µg/L arsenic.
Steven H. Lamm; Hamid Ferdosi; Elisabeth K. Dissen; Ji Li; Jaeil Ahn. A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water. International Journal of Environmental Research and Public Health 2015, 12, 15498 -15515.
AMA StyleSteven H. Lamm, Hamid Ferdosi, Elisabeth K. Dissen, Ji Li, Jaeil Ahn. A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water. International Journal of Environmental Research and Public Health. 2015; 12 (12):15498-15515.
Chicago/Turabian StyleSteven H. Lamm; Hamid Ferdosi; Elisabeth K. Dissen; Ji Li; Jaeil Ahn. 2015. "A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water." International Journal of Environmental Research and Public Health 12, no. 12: 15498-15515.
The ingestion of inorganic arsenic causes bladder and lung cancers demonstrably at >400–500 ug/L but questionably below 100–200 ug/L. Using the standard 42-village cancer mortality dataset from the Blackfoot-disease (BFD) endemic area of southwest Taiwan (Wu et al., 1989), we examined the risk from low exposures by excluding the high exposures. Poisson regression analyses with the sequential removal of the highest exposure village have been performed using the median, mean, or maximum village well water arsenic level and demonstrated graphically. Risk estimates are positive when villages with exposures of 200–400 ug/L are included and significantly so when villages with >400 ug/L are included. Risk estimates for exposures below 100 ug/L are negative but rarely significantly so. The inflection point where the slope is no longer positive occurs in the range of 100–200 ug/L, depending upon whether the exposure metric used is the median, the mean or the maximum. There is a discontinuity in the cancer slope factor or risk from arsenic exposure that occurs in the range of 100–200 ug/L. Above these levels, there are significantly positive risks, while below these levels there are not. The analysis reveals within this dataset an intrinsic non-linearity in the cancer risk. The literature speaks to this discontinuity, but this is the first demonstration within a single dataset that shows the discontinuity across the full exposure range and where the low-dose data are not compromised with high-dose data.
Steven H. Lamm; Shayhan Robbins; Rusan Chen; Jun Lu; Brian Goodrich; Manning Feinleib. Discontinuity in the cancer slope factor as it passes from high to low exposure levels – arsenic in the BFD-endemic area. Toxicology 2014, 326, 25 -35.
AMA StyleSteven H. Lamm, Shayhan Robbins, Rusan Chen, Jun Lu, Brian Goodrich, Manning Feinleib. Discontinuity in the cancer slope factor as it passes from high to low exposure levels – arsenic in the BFD-endemic area. Toxicology. 2014; 326 ():25-35.
Chicago/Turabian StyleSteven H. Lamm; Shayhan Robbins; Rusan Chen; Jun Lu; Brian Goodrich; Manning Feinleib. 2014. "Discontinuity in the cancer slope factor as it passes from high to low exposure levels – arsenic in the BFD-endemic area." Toxicology 326, no. : 25-35.
To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level 500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors.
Steven H. Lamm; Shayhan A. Robbins; Chao Zhou; Jun Lu; Rusan Chen; Manning Feinleib. Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150μg/L) well water arsenic levels – An exploration of the dose–response Poisson analysis. Regulatory Toxicology and Pharmacology 2012, 65, 147 -156.
AMA StyleSteven H. Lamm, Shayhan A. Robbins, Chao Zhou, Jun Lu, Rusan Chen, Manning Feinleib. Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150μg/L) well water arsenic levels – An exploration of the dose–response Poisson analysis. Regulatory Toxicology and Pharmacology. 2012; 65 (1):147-156.
Chicago/Turabian StyleSteven H. Lamm; Shayhan A. Robbins; Chao Zhou; Jun Lu; Rusan Chen; Manning Feinleib. 2012. "Bladder/lung cancer mortality in Blackfoot-disease (BFD)-endemic area villages with low (<150μg/L) well water arsenic levels – An exploration of the dose–response Poisson analysis." Regulatory Toxicology and Pharmacology 65, no. 1: 147-156.
Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD)–endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose–response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 μg/L (95% confidence interval, 42 to 229 μg/L). Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose–response relationship with arsenic exposure by separating out township as a confounding factor.
Steven H. Lamm; Arnold Engel; Cecilia A. Penn; Rusan Chen; Manning Feinleib. Arsenic Cancer Risk Confounder in Southwest Taiwan Data Set. Environmental Health Perspectives 2006, 114, 1077 -1082.
AMA StyleSteven H. Lamm, Arnold Engel, Cecilia A. Penn, Rusan Chen, Manning Feinleib. Arsenic Cancer Risk Confounder in Southwest Taiwan Data Set. Environmental Health Perspectives. 2006; 114 (7):1077-1082.
Chicago/Turabian StyleSteven H. Lamm; Arnold Engel; Cecilia A. Penn; Rusan Chen; Manning Feinleib. 2006. "Arsenic Cancer Risk Confounder in Southwest Taiwan Data Set." Environmental Health Perspectives 114, no. 7: 1077-1082.