Study
PLCO
(Learn more about this study)
Project ID
2009-0518
Initial CDAS Request Approval
Aug 21, 2009
Title
Prospective assessment of thyroid cancer risk and exposure to persistent polyhalogenated aromatic hydrocarbons
Summary
Thyroid cancer incidence has increased significantly over the period 1976-2005 in many countries in both men and women, suggesting an etiologic role for environmental exposures. However, to date, other than ionizing radiation, the causes of thyroid cancer remain relatively obscure. Recent emerging evidence shows that PHAHs, especially polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs), alter thyroid hormone homeostasis and cause thyroid dysfunction; which may subsequently cause thyroid tumorigenesis. Use of PBDEs as fire retardants increased rapidly after 1965 and the U.S. population currently has the highest recorded exposure levels. PCBs and organochlorine insecticides (e.g., DDT, chlordane) became common environmental contaminants after World War II due to their wide use and bioaccumulation through the food chain. We propose to evaluate serum concentrations of these chemicals in relation to thyroid cancer incidence using samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial using a nested case-control design (69 cases, 138 controls). As sample collection for PLCO occurred in the 1990s, it is an ideal cohort for the investigation of PBDEs. The data from PLCO will be combined with data from the CLUE cohort (Campaign Against Cancer and Stroke, sponsored by Johns Hopkins University School of Hygiene and Public Health) which includes samples collected in the mid-70s and late 1980s (60 cases, 120 controls), ideal timing for investigating exposure to PCBs and organochlorine pesticides. The association between analyte levels and thyroid cancer will be estimated using odds ratios (OR) and 95% confidence intervals calculated from conditional logistic regression modeling. This study will have adequate power to detect moderate associations between PBDEs and thyroid cancer (e.g., upper quartile OR of 2.0 or greater) and will increase the power to detect an effect for PCBs and OC pesticides in the CLUE cohort. Our research will provide the first data addressing PHAH exposures and thyroid cancer. This research project has significant implications for improving our understanding of ubiquitous environmental exposures on an increasingly common yet poorly understood cancer.
Aims
The aim of our study is to investigate whether thyroid cancer risk is associated with pre-diagnostic serum levels of: 1. PBDE congeners (7 individual congeners and sum of congeners. The 7 congeners are 2,2´,4,4´- tetrabromodiphenyl ether (BDE-47), 2,2´,3,4,4´-pentaBDE (BDE-85), 2,2´,4,4´,5-pentaBDE (BDE-99), 2,2´,4,4´,6-pentaBDE (BDE-100), 2,2´,4,4´,5,5´-hexaBDE (BDE-153), 2,2´,4,4´,5,6´-hexaBDE (BDE-154), 2,2´,3,4,4´,5´,6-heptaBDE (BDE-183)). 2. PCB congeners (37 individual congeners and sum of congeners) 3. Organochlorine pesticides (p,p'-DDT, p,p'-DDE, p,p'-DDD, o,p'-DDT, o,p'-DDE, chlordanes, methoxychlor, PCP, and HCB). Given that certain PBDEs, PCBs, DDE and HCBs, among other organochlorines, have been shown to decrease serum concentrations of T3 and T4, thus increasing levels of TSH, we hypothesize that disruption of thyroid hormone metabolism from PHAH exposure will be associated with an increased risk of thyroid cancer.
Collaborators
Mary Ward (NCI, DCEG)
Richard Hayes (NCI, DCEG)
Briseis Kilfoy (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
Briseis Kilfoy (DCEG - Other)
Jongeun Rhee (NCI, DCEG)
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