An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas

Abstract

Introduction: Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. Methods: The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. Results: The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). Conclusions: This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

Vinyl Institute Comments on Cicalese et al.: “An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas”

“…Cicalese et al [1] improperly draw conclusions regarding suggested cause and effect from the associations described by the data in their study. The authors derive effects from estimates of ambient vinyl chloride monomer (VCM) that describe only associations based on inconsistent data.…”

“…Table 1 [1] indicates, for example, that VCM was found to have a statistically significant association with HCC using model 1 for data years 2002 and 2005 but not for data years 1996 and 1999. Model 2 indicated that VCM was associated with HCC for all 4 data years.…”

Methodological Limitations to the Analysis by Cicalese et al.

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Dear Editor, This letter is in response to the article "An ecological study of the association between air pollution and hepatocellular carcinoma incidence in Texas" by Cicalese et al [1], where the authors used nonparametric generalized additive logistic regression and gamma regression models to examine the association between county-level concentrations of air pollutants and hepatocellular carcinoma (HCC) incidence rates, concluding that vinyl chloride is a significant contributor to the incidence of HCC in Texas. We believe that these findings are unsubstantiated and misleading given the severe methodological limitations of the paper that we describe below.

As an ecological study, this study is limited by measuring both exposure and outcome at the population level rather than the individual level.

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Response to the Comments on Cicalese et al.: “An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas”

“…In response to the comments [1, 2] regarding the article by Cicalese et al, “An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas” [3], the authors acknowledge minor editorial errors but stand behind the methodology and conclusions of the paper. There appears to be a misunderstanding concerning what these data and results suggest; we aim to clarify these points and respond to critiques that the authors knowingly published results based on limited assumptions.…”

“…Quoted material is reproduced from either the comments submitted to the editor [1, 2] (numbered) or the published paper [3] (bulleted).…”