br Corresponding author at Department of Epidemiology and Bi
Corresponding author at: Department of Epidemiology and Biostatistics, University of California San Francisco, 2001 Center Street, Suite 700, Berkeley, CA 94704, USA. E-mail address: [email protected] (S. Hurley).
the environment. Owing to their highly persistent and bioaccumulative nature, they have become major persistent organic pollutants (POPs), detected in nearly all environmental media tested, as well as in wildlife and human tissue (Betts, 2008; Costa et al., 2008; Darnerud et al., 2001; Environmental Working Group, 2007; Hites, 2004; Lorber, 2008; United States Environmental Protection Agency, 2008; Sjodin et al., 2008).
Interest in the PBDEs as potential human carcinogens stems from their similar structure and toxicological properties to polychlorinated biphenyls (PCBs), which are known human chemical carcinogens (Betts, 2008; Lorber, 2008; McDonald, 2002; Siddiqi et al., 2003; Lauby-Secretan et al., 2013). Moreover, interest in breast cancer, which is a hormonally-mediated disease, has been driven by a substantial body of laboratory evidence demonstrating endocrine-disrupting effects of PBDEs, including the ability to alter in vivo circulating sex hormone concentrations, enhance estrogenic-like cellular proliferation in MCF-7 cell lines, and interact with A 61603 and androgen signaling pathways (Costa et al., 2008; Darnerud, 2008; Gregoraszczuk et al., 2008; Hamers et al., 2006; He et al., 2008; Meerts et al., 2001; Mercado-Feliciano and Bigsby, 2008a, 2008b; Talsness, 2008; Talsness et al., 2008; Legler, 2008; Lyche et al., 2015; Karpeta and Gregoraszczuk, 2017; Karpeta et al., 2016; Kwiecinska et al., 2011). None of the PBDEs have been formally evaluated for carcinogenicity by the International Agency for Research on Cancer. Only one PBDE congener (BDE-209) has been evaluated by the United States Environmental Protection Agency (US EPA), which classified it as a ‘suggestive’ human carcinogen in 2008 (U.S. Environmental Protection Agency, 2008). More recently, how-ever, the US National Toxicology Program conducted a rodent bioassay for a mixture of BDEs consisting of BDE-47, BDE-99 and BDE-153 (predominant congeners in what was once the most-commonly used commercial BDE formulation) and concluded there was ‘clear evidence of carcinogenicity’, primarily based on associations found with several hepatic cancers in rodent models (U.S. Environmental Protection Agency (EPA), 2017; US Department of Health and Human Services, 2015). r> Human data are sparse. Only a handful of small case-control studies have evaluated PBDEs and cancer risk. Increased risks have been re-ported for testicular cancer (Hardell et al., 2006) and childhood acute lymphoblastic leukemia (Ward et al., 2014). The epidemiologic evi-dence for thyroid cancer is smooth muscle mixed, with one studying reporting no as-sociation (Aschebrook-Kilfoy et al., 2015) while another reporting elevated risks associated with BDE-209 measured in household dust (Hoffman et al., 2017). Neither of the two small breast cancer studies conducted to date found a significant association with PBDEs (Holmes et al., 2014; Hurley et al., 2011).
The objective of the current study was to evaluate the risk of in-vasive breast cancer associated with serum PBDE levels among 1838 women participating in a case-control study nested within the California Teachers Study (CTS) cohort.
2. Materials and methods
2.1. Study population
The study participants were drawn from the CTS, an on-going pro-spective cohort study of 133,479 female California public school pro-fessionals initiated in 1995–1996 primarily to study breast cancer. Details of the creation and conduct of the CTS are published elsewhere (Bernstein et al., 2002). Briefly, since the CTS was established via re-sponses to a mailed questionnaire, the cohort has been followed an-nually for cancer diagnoses, deaths, and changes of address. State and national mortality files, as well as reports from relatives, are used to ascertain dates and causes of death. Address changes for continued follow-up are obtained by several methods including annual mailings, notifications of moves received from participants, and linkages to na-tionwide consumer reporting companies and the U.S. Postal Service