DESCRIPTION (provided by applicant):
The purpose of this study is to investigate the cancer risk in Michigan residents who were exposed to varying (including high) levels of polybrominated biphenyls (PBBs - a fire retardant) from 1973-74 through an accidental exposure in food. PBBs may have endocrine disrupting potential and other environmentally persistent organohalogens such as polybrominated diphenyl ether (PBDEs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (such as DDT and DDE) have also been thought to have this property. These compounds may affect cancer risk, as has been suggested by an initial finding of a nonsignificant increase in breast cancer risk in the Michigan PBB Cohort and other epidemiologic study results. This study will utilize an epidemiologic cohort design to determine whether PBBs increase the risk of cancers at specific sites and whether there is a dose-response relationship between serum PBB levels and the relative risk of site-specific cancers. The participants in this study had serum PBB measurements obtained shortly after the accidental exposure and at later times. Cancer incidence in the cohort will be determined by linking to the Michigan Cancer and Death Registries. The first specific aim of this investigation is to determine whether the observed number of primary cancers at specific and grouped cancer sites in the cohort, are higher than expected based on (i) rates in rural Michigan counties where cohort members resided and (ii) national rates using data from the Surveillance, Epidemiology, and End Results Registries (SEER) by calculating standardized incidence ratios (SIRs). Secondly, we will determine whether the risk of common cancers is increased in subjects in the cohort who have higher baseline serum PBB levels using Poisson Regression. In addition, we will determine whether the risk of breast and prostate cancer is related to baseline serum PBB levels using nested case-control designs. In the breast cancer nested case-control study, we will utilize two additional data sets to determine whether additional variables may confound the PBB-breast cancer relationship. Furthermore, if significant, the results of the proposed project will serve as pilot data for expanded, mechanism-focused nested case-control studies of breast, prostate, or other cancers displaying an association with PBB exposure. These studies could involve performing in-person interviews and obtaining biologic samples (such as blood samples or cheek swabs) to determine the mechanism of a potential carcinogenic effect. This proposed study will provide information on the potential carcinogenic effects of a range of exposure levels to an organohalogen (PBBs) in a well-characterized cohort population. Information from this investigation can be applied to research on other environmentally persistent organohalogens with similar structures which are of public health concern, such as PCBs, DDT/DDE, and brominated flame retardants (PBDEs).
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