Serum Organochlorine Levels and Metastatic Prostate Cancer
Serum Organochlorine Levels and Metastatic Prostate Cancer
Background: Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.
Objectives: We conducted a nested case–control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.
Methods: Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.
Results: Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log–transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).
Conclusions: Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.
Organochlorines (OCs) are a diverse group of persistent synthetic compounds that have been used as pesticides (mostly insecticides) and for various industrial and commercial applications.
OC insecticides were widely used in agriculture and pest control between the 1940s and 1960s. Another group of OC compounds, polychlorinated biphenyls (PCBs), were historically used in numerous construction materials including plasticizers, adhesives, flame retardants, caulk, sealants, and paints, and in electrical equipment. These compounds resist degradation, bioaccumulate in adipose tissue of humans and other tissues, and persist in the environment. Many countries banned their production in the 1970s and 1980s, citing public health concerns (Longnecker et al. 1997). Evidence suggests that some of these OC compounds may cause a variety of adverse health effects, including cancer. The International Agency for Research on Cancer (IARC) lists PCBs as carcinogenic to humans (Group 1) (Lauby-Secretan et al. 2013) although the assessment for the OC insecticides is less clear, with some specific insecticides listed as possible human carcinogens (Group 2B), and others listed as not classifiable (Group 3) (IARC 1991).
The mechanisms by which OC compounds might influence cancer development are not completely understood; however, many of the chemicals have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties (IARC 2012; Longnecker et al. 1997). Because of this, the impact of exposure to these compounds on risk of hormonal cancers, such as prostate cancer, is a concern. Several studies have reported associations between exposures to these compounds and prostate cancer among occupationally exposed populations (Prince et al. 2006; Purdue et al. 2007; Van Maele-Fabry and Willems 2004), but there is less information about associations with environmental exposures in the general population, which occur mainly from meat, fish, and dairy consumption (Kvalem et al. 2009; Schecter et al. 2010). Associations of environmental OC exposures and prostate cancer have been evaluated in eight epidemiologic studies (one ecologic study, one cross-sectional study, and six case–control studies) (Aronson et al. 2010; Hardell et al. 2006; Kumar et al. 2010; Multigner et al. 2010; Pavuk et al. 2004; Ritchie et al. 2003, 2005; Sawada et al. 2010; Xu et al. 2010). A small hospital-based case–control study from the United States reported positive associations of PCB congener 180 and the chlordane metabolite oxychlordane with prostate cancer (Ritchie et al. 2003). Another hospital-based study from Sweden showed significant positive associations between PCB 153 and the chlordane constituent trans-chlordane and prostate cancer (Hardell et al. 2006). Two additional studies have shown statistically significant positive associations of other OC insecticides, including chlordecone, β-hexachlorocyclohexane (HCH), and γ-HCH with prostate cancer (Kumar et al. 2010; Multigner et al. 2010). Conversely, two studies, including the only study to use prospectively collected serum, have reported inverse associations of prostate cancer with total PCBs overall, certain PCB congeners, and the OC insecticides β-HCH and γ-HCH (Aronson et al. 2010; Sawada et al. 2010).
Given these mixed results, we conducted a nested case–control study, using serum collected prior to diagnosis, to evaluate associations between environmental OC exposures and metastatic prostate cancer in the population-based Janus Serum Bank cohort of Norway.
Abstract and Introduction
Abstract
Background: Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern.
Objectives: We conducted a nested case–control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway.
Methods: Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression.
Results: Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log–transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02).
Conclusions: Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer.
Introduction
Organochlorines (OCs) are a diverse group of persistent synthetic compounds that have been used as pesticides (mostly insecticides) and for various industrial and commercial applications.
OC insecticides were widely used in agriculture and pest control between the 1940s and 1960s. Another group of OC compounds, polychlorinated biphenyls (PCBs), were historically used in numerous construction materials including plasticizers, adhesives, flame retardants, caulk, sealants, and paints, and in electrical equipment. These compounds resist degradation, bioaccumulate in adipose tissue of humans and other tissues, and persist in the environment. Many countries banned their production in the 1970s and 1980s, citing public health concerns (Longnecker et al. 1997). Evidence suggests that some of these OC compounds may cause a variety of adverse health effects, including cancer. The International Agency for Research on Cancer (IARC) lists PCBs as carcinogenic to humans (Group 1) (Lauby-Secretan et al. 2013) although the assessment for the OC insecticides is less clear, with some specific insecticides listed as possible human carcinogens (Group 2B), and others listed as not classifiable (Group 3) (IARC 1991).
The mechanisms by which OC compounds might influence cancer development are not completely understood; however, many of the chemicals have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties (IARC 2012; Longnecker et al. 1997). Because of this, the impact of exposure to these compounds on risk of hormonal cancers, such as prostate cancer, is a concern. Several studies have reported associations between exposures to these compounds and prostate cancer among occupationally exposed populations (Prince et al. 2006; Purdue et al. 2007; Van Maele-Fabry and Willems 2004), but there is less information about associations with environmental exposures in the general population, which occur mainly from meat, fish, and dairy consumption (Kvalem et al. 2009; Schecter et al. 2010). Associations of environmental OC exposures and prostate cancer have been evaluated in eight epidemiologic studies (one ecologic study, one cross-sectional study, and six case–control studies) (Aronson et al. 2010; Hardell et al. 2006; Kumar et al. 2010; Multigner et al. 2010; Pavuk et al. 2004; Ritchie et al. 2003, 2005; Sawada et al. 2010; Xu et al. 2010). A small hospital-based case–control study from the United States reported positive associations of PCB congener 180 and the chlordane metabolite oxychlordane with prostate cancer (Ritchie et al. 2003). Another hospital-based study from Sweden showed significant positive associations between PCB 153 and the chlordane constituent trans-chlordane and prostate cancer (Hardell et al. 2006). Two additional studies have shown statistically significant positive associations of other OC insecticides, including chlordecone, β-hexachlorocyclohexane (HCH), and γ-HCH with prostate cancer (Kumar et al. 2010; Multigner et al. 2010). Conversely, two studies, including the only study to use prospectively collected serum, have reported inverse associations of prostate cancer with total PCBs overall, certain PCB congeners, and the OC insecticides β-HCH and γ-HCH (Aronson et al. 2010; Sawada et al. 2010).
Given these mixed results, we conducted a nested case–control study, using serum collected prior to diagnosis, to evaluate associations between environmental OC exposures and metastatic prostate cancer in the population-based Janus Serum Bank cohort of Norway.
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