The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Evaluating for a Geospatial Relationship Between Radon Levels and Thyroid Cancer in Pennsylvania Neerav Goyal, MD, MPH; Fabian Camacho, MS, MA; Joseph Mangano, MPH, MBA; David Goldenberg, MD, FACS Objectives/Hypothesis: To determine whether there is an association between radon levels and the rise in incidence of thyroid cancer in Pennsylvania. Study Design: Epidemiological study of the state of Pennsylvania. Methods: We used information from the Pennsylvania Cancer Registry and the Pennsylvania Department of Energy. From the registry, information regarding thyroid incidence by county and zip code was recorded. Information regarding radon levels per county was recorded from the state. Poisson regression models were fit predicting county-level thyroid incidence and change as a function of radon/lagged radon levels. To account for measurement error in the radon levels, a Bayesian Model extending the Poisson models was fit. Geospatial clustering analysis was also performed. Results: No association was noted between cumulative radon levels and thyroid incidence. In the Poisson modeling, no significant association was noted between county radon level and thyroid cancer incidence (P 5.23). Looking for a lag between the radon level and its effect, no significant effect was seen with a lag of 0 to 6 years between exposure and effect (P 5.063 to P 5.59). The Bayesian models also failed to show a statistically significant association. A cluster of high thyroid cancer incidence was found in western Pennsylvania. Conclusions: Through a variety of models, no association was elicited between annual radon levels recorded in Pennsylvania and the rising incidence of thyroid cancer. However, a cluster of thyroid cancer incidence was found in western Pennsylvania. Further studies may be helpful in looking for other exposures or associations. Key Words: Ecological study, radon, thyroid cancer, Pennsylvania, geospatial clustering. Level of Evidence: NA Laryngoscope, 125:E45–E49, 2015
INTRODUCTION One of the few known environmental associations with thyroid cancer is a history of radiation exposure. Ionizing radiation in particular has been associated with a variety of cancers (colorectal, parotid, sarcomas). It is defined as particles (such as x-rays, a-rays, b-rays, crays) with enough energy to remove an electron from an atom or molecule, thus creating an ion. These ions and free radicals can cause damage to DNA and in effect initiate tumorigenesis. This effect has an established carcinogenic potential thought to occur in a dose-dependent fashion. Incidents with large releases of ionizing radiaFrom the Pennsylvania State University–Milton S. Hershey Medical Center (N.G., FC., D.G.); Department of Surgery, Division of Otolaryngology–Head and Neck Surgery (N.G., D.G.); Department of Public Health Sciences, Division of Health Sciences Research (F.C.); and the Radiation and Public Health Project (J.M.), The Pennsylvania State University, Hershey, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication June 4, 2014. This work was funded by the 2012 AHNS Alando J. Ballantyne Resident Research Pilot Grant (CORE grant). The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Neerav Goyal, MD, Division of Otolaryngology–Head & Neck Surgery, Department of Surgery, The Pennsylvania State University–Milton S. Hershey Medical Center, 500 University Drive, Mail Code H091, Hershey, PA 17033-0850. E-mail: [email protected] DOI: 10.1002/lary.24815
Laryngoscope 125: January 2015
tion, such as the atomic bomb sites of Hiroshima and Nagasaki,1–3 as well as the Chernobyl nuclear plant disaster,4–8 have shown an increased risk of cancer, including thyroid cancer, in the radiation-exposed populations. Another source of radiation is radon. Radon is a colorless, odorless, tasteless radioactive gas that is a decay product of uranium in the soil. It decays via ionizing radiation with the release of a particles. Additionally, as a gas, it is easily inhaled, and its decay products can layer the aerodigestive tract. More recent ecological studies have evaluated the possible association with environmental exposure to radon and cancer. An ecological study performed in Portugal concluded that 18% to 28% of lung cancer mortality could be attributed to indoor radon exposure after accounting for smoking habits.9 Additionally, radon was found to be significantly associated with chronic obstructive pulmonary disease mortality in Canada.10 An ecological study using postal codes in southwest England also found an exposureresponse relationship between residential radon levels and squamous cell carcinoma.11 Kendall et al. have also described that radon and its byproducts can affect multiple organs in the body via inhalation of the gas as well as by transport of the gas through the blood stream.12 Although ionizing radiation exposure from a single event (such as Chernobyl) has an established association with thyroid cancer, the majority of patients seen with thyroid neoplasms have no history of ionizing radiation Goyal et al.: Radon and Thyroid Cancer
E45
exposure. The data released by Pennsylvania and the United States display an unexplained increase in the incidence of thyroid cancer, with a more rapid increase in incidence between 1996 and 2005, than any other cancer site. Additionally, among the states, Pennsylvania has one of the highest incidences and rises in incidences of thyroid cancer.13 Currently, there is no explanation for this discrepancy in Pennsylvania or the United States. Given the historical nuclear accident in central Pennsylvania with Three Mile Island, recent research has evaluated whether this accident has a correlation with thyroid cancer in the state. These studies did not find an association or causal relationship between the Three Mile Island nuclear reactor and the prevalence of thyroid cancer in the state, though there may be a higher incidence of thyroid cancer than expected in the area.13–15 Previous literature has shown that ionizing radiation is associated with thyroid cancer.7,16 Additionally, the ingestion and inhalation of radiation products has been shown to be correlated with thyroid cancer.16 Given the high rates of radon levels in Pennsylvania and the link between radon exposure (both via inhalation and through the bloodstream) and carcinogenesis,12,17 we hypothesize that there may be an association between thyroid cancer and radon exposure. This study evaluated the levels of radon evident in Pennsylvania to determine whether any correlations exist between radon and the incidence of thyroid cancer in the state.
MATERIALS AND METHODS Institutional review board approval was obtained from The Pennsylvania State University–Milton S. Hershey Medical Center for this study. Publicly available deidentified databases as well as thirdparty databases were used for the study. The Pennsylvania Cancer Registry is a publicly available database of new cases of cancer diagnosed or treated within Pennsylvania, beginning in 1985, including data compiled from hospitals, clinics, laboratories, radiation facilities, surgical centers, cancer centers, doctors’ offices, death certificates, as well as information exchange when Pennsylvania residents are diagnosed or treated in other states. It serves as a representative population for retrospective studies, such as this one, due to its comprehensive nature. Data were collected from the Pennsylvania Cancer Registry, which provided information on each case of thyroid cancer diagnosed in Pennsylvania residents from 1991 to 2009. Thyroid cancer was identified by an International Classification of Diseases for Oncology 2 and 3 primary site code of C739. Using crude rates as well as county information for each case obtained through the registry, this information was used to calculate thyroid cancer incidence for each geographic area in Pennsylvania. Radon levels were measured in picocuries per liter of air. Through third-party radon testing agencies, the Pennsylvania Department of Environmental Protection accumulates and aggregates county level data on radon levels. This information is obtained by self-testing kits that are used and sent in by homeowners and businesses in the state. Information was obtained from the agency for the years 1991 to 2009. Additional similar information was obtained from a third-party agency (Air Check, Inc., Mills River, NC) for the years 1995 to 2009.
Laryngoscope 125: January 2015
E46
In performing an analysis of the data, county-level comparisons were made. We began by assuring data reliability by comparing our two sources of radon level data to confirm correlation between the datasets. This was done by performing a Pearson correlation between the two datasets. Additionally, radon measurements from previous years were compared to more recent years via a relative ranking method to determine whether there is consistency between measurements. After assessing the reliability of the data, a variety of models were fit to assess the correlation, if any, between thyroid cancer incidence and radon levels. A Poisson regression model with random effects was fit to the log of the expected thyroid cases for a specific year and county using the dependent variables of radon rate, log total population, year effect, as well as a random variable from a normal distribution to assess county effect. Additional models were created to assess for possible overdispersion in the event of predictors that were not accounted for, as well as to include the previous year’s thyroid incidence and a possible lag effect of radon on thyroid cancer. A Bayesian model was also fit to the data to account for possible unreliability in the radon measurements. A final Poisson model was fit to the third-party data to determine if a difference in fit was evident in the two radon datasets. Significance was determined with an acceptable Type I error of a 5 .05, with a P
Rhinological and Otological Society, Inc.
Evaluating for a Geospatial Relationship Between Radon Levels and Thyroid Cancer in Pennsylvania Neerav Goyal, MD, MPH; Fabian Camacho, MS, MA; Joseph Mangano, MPH, MBA; David Goldenberg, MD, FACS Objectives/Hypothesis: To determine whether there is an association between radon levels and the rise in incidence of thyroid cancer in Pennsylvania. Study Design: Epidemiological study of the state of Pennsylvania. Methods: We used information from the Pennsylvania Cancer Registry and the Pennsylvania Department of Energy. From the registry, information regarding thyroid incidence by county and zip code was recorded. Information regarding radon levels per county was recorded from the state. Poisson regression models were fit predicting county-level thyroid incidence and change as a function of radon/lagged radon levels. To account for measurement error in the radon levels, a Bayesian Model extending the Poisson models was fit. Geospatial clustering analysis was also performed. Results: No association was noted between cumulative radon levels and thyroid incidence. In the Poisson modeling, no significant association was noted between county radon level and thyroid cancer incidence (P 5.23). Looking for a lag between the radon level and its effect, no significant effect was seen with a lag of 0 to 6 years between exposure and effect (P 5.063 to P 5.59). The Bayesian models also failed to show a statistically significant association. A cluster of high thyroid cancer incidence was found in western Pennsylvania. Conclusions: Through a variety of models, no association was elicited between annual radon levels recorded in Pennsylvania and the rising incidence of thyroid cancer. However, a cluster of thyroid cancer incidence was found in western Pennsylvania. Further studies may be helpful in looking for other exposures or associations. Key Words: Ecological study, radon, thyroid cancer, Pennsylvania, geospatial clustering. Level of Evidence: NA Laryngoscope, 125:E45–E49, 2015
INTRODUCTION One of the few known environmental associations with thyroid cancer is a history of radiation exposure. Ionizing radiation in particular has been associated with a variety of cancers (colorectal, parotid, sarcomas). It is defined as particles (such as x-rays, a-rays, b-rays, crays) with enough energy to remove an electron from an atom or molecule, thus creating an ion. These ions and free radicals can cause damage to DNA and in effect initiate tumorigenesis. This effect has an established carcinogenic potential thought to occur in a dose-dependent fashion. Incidents with large releases of ionizing radiaFrom the Pennsylvania State University–Milton S. Hershey Medical Center (N.G., FC., D.G.); Department of Surgery, Division of Otolaryngology–Head and Neck Surgery (N.G., D.G.); Department of Public Health Sciences, Division of Health Sciences Research (F.C.); and the Radiation and Public Health Project (J.M.), The Pennsylvania State University, Hershey, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication June 4, 2014. This work was funded by the 2012 AHNS Alando J. Ballantyne Resident Research Pilot Grant (CORE grant). The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Neerav Goyal, MD, Division of Otolaryngology–Head & Neck Surgery, Department of Surgery, The Pennsylvania State University–Milton S. Hershey Medical Center, 500 University Drive, Mail Code H091, Hershey, PA 17033-0850. E-mail: [email protected] DOI: 10.1002/lary.24815
Laryngoscope 125: January 2015
tion, such as the atomic bomb sites of Hiroshima and Nagasaki,1–3 as well as the Chernobyl nuclear plant disaster,4–8 have shown an increased risk of cancer, including thyroid cancer, in the radiation-exposed populations. Another source of radiation is radon. Radon is a colorless, odorless, tasteless radioactive gas that is a decay product of uranium in the soil. It decays via ionizing radiation with the release of a particles. Additionally, as a gas, it is easily inhaled, and its decay products can layer the aerodigestive tract. More recent ecological studies have evaluated the possible association with environmental exposure to radon and cancer. An ecological study performed in Portugal concluded that 18% to 28% of lung cancer mortality could be attributed to indoor radon exposure after accounting for smoking habits.9 Additionally, radon was found to be significantly associated with chronic obstructive pulmonary disease mortality in Canada.10 An ecological study using postal codes in southwest England also found an exposureresponse relationship between residential radon levels and squamous cell carcinoma.11 Kendall et al. have also described that radon and its byproducts can affect multiple organs in the body via inhalation of the gas as well as by transport of the gas through the blood stream.12 Although ionizing radiation exposure from a single event (such as Chernobyl) has an established association with thyroid cancer, the majority of patients seen with thyroid neoplasms have no history of ionizing radiation Goyal et al.: Radon and Thyroid Cancer
E45
exposure. The data released by Pennsylvania and the United States display an unexplained increase in the incidence of thyroid cancer, with a more rapid increase in incidence between 1996 and 2005, than any other cancer site. Additionally, among the states, Pennsylvania has one of the highest incidences and rises in incidences of thyroid cancer.13 Currently, there is no explanation for this discrepancy in Pennsylvania or the United States. Given the historical nuclear accident in central Pennsylvania with Three Mile Island, recent research has evaluated whether this accident has a correlation with thyroid cancer in the state. These studies did not find an association or causal relationship between the Three Mile Island nuclear reactor and the prevalence of thyroid cancer in the state, though there may be a higher incidence of thyroid cancer than expected in the area.13–15 Previous literature has shown that ionizing radiation is associated with thyroid cancer.7,16 Additionally, the ingestion and inhalation of radiation products has been shown to be correlated with thyroid cancer.16 Given the high rates of radon levels in Pennsylvania and the link between radon exposure (both via inhalation and through the bloodstream) and carcinogenesis,12,17 we hypothesize that there may be an association between thyroid cancer and radon exposure. This study evaluated the levels of radon evident in Pennsylvania to determine whether any correlations exist between radon and the incidence of thyroid cancer in the state.
MATERIALS AND METHODS Institutional review board approval was obtained from The Pennsylvania State University–Milton S. Hershey Medical Center for this study. Publicly available deidentified databases as well as thirdparty databases were used for the study. The Pennsylvania Cancer Registry is a publicly available database of new cases of cancer diagnosed or treated within Pennsylvania, beginning in 1985, including data compiled from hospitals, clinics, laboratories, radiation facilities, surgical centers, cancer centers, doctors’ offices, death certificates, as well as information exchange when Pennsylvania residents are diagnosed or treated in other states. It serves as a representative population for retrospective studies, such as this one, due to its comprehensive nature. Data were collected from the Pennsylvania Cancer Registry, which provided information on each case of thyroid cancer diagnosed in Pennsylvania residents from 1991 to 2009. Thyroid cancer was identified by an International Classification of Diseases for Oncology 2 and 3 primary site code of C739. Using crude rates as well as county information for each case obtained through the registry, this information was used to calculate thyroid cancer incidence for each geographic area in Pennsylvania. Radon levels were measured in picocuries per liter of air. Through third-party radon testing agencies, the Pennsylvania Department of Environmental Protection accumulates and aggregates county level data on radon levels. This information is obtained by self-testing kits that are used and sent in by homeowners and businesses in the state. Information was obtained from the agency for the years 1991 to 2009. Additional similar information was obtained from a third-party agency (Air Check, Inc., Mills River, NC) for the years 1995 to 2009.
Laryngoscope 125: January 2015
E46
In performing an analysis of the data, county-level comparisons were made. We began by assuring data reliability by comparing our two sources of radon level data to confirm correlation between the datasets. This was done by performing a Pearson correlation between the two datasets. Additionally, radon measurements from previous years were compared to more recent years via a relative ranking method to determine whether there is consistency between measurements. After assessing the reliability of the data, a variety of models were fit to assess the correlation, if any, between thyroid cancer incidence and radon levels. A Poisson regression model with random effects was fit to the log of the expected thyroid cases for a specific year and county using the dependent variables of radon rate, log total population, year effect, as well as a random variable from a normal distribution to assess county effect. Additional models were created to assess for possible overdispersion in the event of predictors that were not accounted for, as well as to include the previous year’s thyroid incidence and a possible lag effect of radon on thyroid cancer. A Bayesian model was also fit to the data to account for possible unreliability in the radon measurements. A final Poisson model was fit to the third-party data to determine if a difference in fit was evident in the two radon datasets. Significance was determined with an acceptable Type I error of a 5 .05, with a P
