Elsevier

Environmental Research

Volume 165, August 2018, Pages 125-132
Environmental Research

A nested case-control study of polychlorinated biphenyls, organochlorine pesticides, and thyroid cancer in the Janus Serum Bank cohort

https://doi.org/10.1016/j.envres.2018.04.012Get rights and content

Highlights

  • First study of pre-diagnostic organochlorine compounds in serum and thyroid cancer.

  • p,p′-DDE (DDT metabolite) inversely associated with thyroid cancer.

  • Birth cohort may be an effect modifier.

  • Some PCBs associated with thyroid cancer in youngest birth cohort.

  • Chlordane metabolites associated with thyroid cancer in youngest birth cohort.

Abstract

Background

Polychlorinated biphenyls (PCBs) and organochlorine pesticides have been associated with altered thyroid hormone levels in humans, but their relationship with thyroid cancer is unknown.

Methods

We conducted a nested case-control study of thyroid cancer in the Norwegian Janus Serum Bank cohort using pre-diagnostic blood samples from 1972 to 1985. Incident thyroid cancer (n = 108) was ascertained through 2008. Controls were matched 2:1 by age, date of blood draw, gender, and county. We used gas chromatography/mass spectrometry to quantify 36 PCB congeners and metabolites of pesticides DDT, chlordane, hexachlorocyclohexane, and hexachlorobenzene. PCBs and pesticide metabolites were evaluated individually and summed by degree of chlorination and parent compound, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression per specified increase in lipid-adjusted concentration. We additionally stratified analyses by birth cohort (1923–1932, 1933–1942, 1943–1957).

Results

Increasing concentration of DDT metabolites (ORper 1000 ng/g = 0.80, 95%CI = 0.66–0.98) was inversely associated with thyroid cancer. Associations for PCBs were null or in inverse direction. We observed interactions for total PCBs, moderately-chlorinated PCBs, and chlordane metabolites with birth cohort (p ≤ 0.04). Among participants born 1943–1957, total PCBs (ORper 100 ng/g = 1.25, 95%CI = 1.00–1.56), moderately-chlorinated PCBs (ORper 100 ng/g = 1.31, 95%CI = 1.01–1.70), and chlordane metabolites (ORper 10 ng/g = 1.78, 95%CI = 1.09–2.93) were positively associated with thyroid cancer. For individuals born before 1943, associations were generally null or in the inverse direction.

Conclusions

Emissions of PCBs and OC pesticides varied over time. Different risk patterns by birth cohort suggest the potential importance of timing of exposure in thyroid cancer risk. Further evaluation of these associations is warranted.

Introduction

Thyroid cancer is one of the most commonly diagnosed cancers among women in the United States (US), and incidence rates among both men and women have increased 211% since 1975 (Lim et al., 2017, Siegel et al., 2017). These patterns are not unique to the US; studies show that thyroid cancer rates have increased in most developed and developing countries worldwide (Engholm et al., 2010, Kilfoy et al., 2009). While increased detection of small, non-aggressive tumors may in part explain this upward trend, a growing body of literature has demonstrated that incidence rates for larger and advanced-stage thyroid cancers are also rising (Enewold et al., 2009, Lim et al., 2017).

Organochlorine (OC) compounds are man-made organic substances that contain one or more chlorine atoms, and include polychlorinated biphenyls (PCBs) and OC pesticides (Pelletier et al., 2003). Due to their chemical structure, OCs are both stable and lipophilic (Kutz et al., 1991); they have long half-lives and may persist in the environment and adipose tissue for many years (Pelletier et al., 2003). PCBs were manufactured beginning in 1929, and production peaked in the 1950–1970s (International Agency for Research on Cancer, 2016). They were widely used in industry as dielectric fluids in capacitors and transformers, and commercially as elastic sealants, flame-retardant coatings, and in other household items such as paints, finishes, and light fixtures (International Agency for Research on Cancer, 2016, DellaValle et al., 2013). PCB use was banned in most countries by the 1980s due to concerns about toxicity and environmental persistence (Environmental Protection Agency, 1979, Füll, 2001, Kutz et al., 1991). After World War II, OC pesticides were used globally for pest control until the 1960–1970s, when most were banned primarily due to environmental concerns (Kutz et al., 1991). Dichlorodiphenyltrichloroethane (DDT) is a well-known OC insecticide that was used widely in agriculture, and still has limited use for the eradication of vector-borne diseases such as malaria (Loomis et al., 2015). Chlordane was used residentially on lawns and shrubbery, in agriculture for common crops such as corn and potatoes, and by professional applicators for eradication of termites (International Agency for Research on Cancer, 2001). Occupational exposures to PCBs (e.g. capacitor manufacturing, construction or demolition) and OC pesticides (e.g. agriculture) were historically a source of exposure in certain industries and may still play a small role (DellaValle et al., 2015, Kutz et al., 1991). However, diet is the most common route of exposure for the general population, particularly through consumption of contaminated fatty foods such as fish, meat, and dairy products (Pelletier et al., 2003).

Many PCBs and OC pesticides have demonstrated thyroid hormone-disrupting effects in laboratory and cross-sectional molecular epidemiologic studies (Brouwer et al., 1999, Brucker-Davis, 1998, Langer, 2010). Studies in laboratory animals have found that exposure to PCB mixtures and specific OC pesticides (i.e. chlordane, hexachlorobenzene [HCB]) increased incidence of thyroid tumors (International Agency for Research on Cancer, 2001, International Agency for Research on Cancer, 2016). Few epidemiologic studies have assessed associations between environmental exposure to OCs and thyroid cancer, with mixed findings. Spanish residents living near a factory producing chlorinated organic compounds had excess thyroid cancer incidence compared to the rest of the province (Grimalt et al., 1994). The authors attributed the association to the high levels of HCB in the sera of residents living near the factory, which was being emitted as a by-product in the production of other OCs. In Slovakia, thyroid cancer incidence rates were lower among women, but not men, residing near a PCB production facility compared to a similar nearby population with substantially lower levels of environmental contamination (Pavuk et al., 2004). A small cohort study of fishermen in upstate New York in an area with known PCB contamination used extensive information on the amount and type of consumption of local fish to evaluate PCB exposure and thyroid cancer risk (Haslam et al., 2016). The authors found an inverse association with thyroid cancer risk, though they attributed this association not to PCBs but to the high omega-3 fatty acid content of fish, high consumption of which has been associated with reduced risk of some cancers (Tavani et al., 2003). Some evidence has emerged from occupational settings as well, such as excess thyroid cancer mortality among capacitor manufacturing workers with occupational exposure to PCBs (Mallin et al., 2004). However, the applicability of these occupational findings to exposures in the general population, where route of exposure, PCB congener mixture, and dose may differ, is unclear.

These prior epidemiologic studies of OCs and thyroid cancer used indirect measures of exposure and had limited power due to small numbers of cases. To our knowledge, no published study has examined pre-diagnostic serum concentrations of PCBs or OC pesticide metabolites and thyroid cancer. To address the hypothesis that these chemicals may influence thyroid cancer risk, we conducted a nested case-control study of thyroid cancer within the Janus Serum Bank Cohort in Norway.

Section snippets

Study population

The Janus Serum Bank Cohort was established in 1973 with funding from the Norwegian Cancer Society for the purposes of conducting cancer research. The cohort recruitment, specimen collection, and participant characteristics has been described (Langseth et al., 2017). Briefly, blood specimens from the Janus Cohort (n = 318,628 individuals) came from two main sources: participants in the Norwegian Regional Health Studies in selected counties in Norway (~90%), and Red Cross blood donors (~10%)

Results

Our study population consisted of 108 thyroid cancer cases and 216 matched controls (Table 1). Over 85% of thyroid cancers in our study were papillary thyroid cancers (n = 92); most of the rest were follicular thyroid cancers. Most thyroid cancer cases were diagnosed between the ages of 51–65, with a median age of 59 years. The median age at blood draw was 41 years, and participants were followed for a median of 21 years. Cases and controls did not differ by the matching characteristics

Discussion

In this first published study to examine pre-diagnostic serum concentrations of PCBs and OC pesticides and thyroid cancer, we found an inverse association for p,p′-DDE, the DDT metabolite found in serum at the highest concentrations. We also observed interactions with birth cohort. Among individuals in the youngest birth cohort (1943–1957), we observed positive associations with increasing concentrations of total PCBs, moderately-chlorinated PCBs, and metabolites of the insecticide chlordane,

Acknowledgement

We thank the Norwegian Cancer Society and Cancer Registry of Norway for their participation in this project.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.

Funding source

This research was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute [Z01 CP010125-22].

Human subjects protections

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