Persistent organic pollutants and mammographic density
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Non-technical overview of the research topic and relevance to breast cancer: Persistent Organic Pollutants (POPs) are a large, diverse group of synthetic compounds that are highly toxic, accumulate in the food chain and human body, and persist in the environment for decades. Extensive laboratory data have suggested a cancer-causing and estrogenic potential of POPs. Estrogens are sex-steroid hormones that are known to elevate breast cancer risk. Thus, existing laboratory data support that POPs may cause breast cancer. However, human data have been inconsistent and largely limited to earlier classes of POPs. In particular, newer classes of POPs that have been extensively used in a variety of commercial products as waterproof and non-stick coatings or as flame retardants in plastics and furniture, have rarely been studied in relation to breast cancer risk. Given that POPs are widely used and we cannot control our exposure to these chemicals as individuals, it is essential to investigate human breast cancer impact of these chemicals. 
 
 
 
 
 
 
 
 Women’s exposure to POPs could occur from diverse sources in complicated ways; thus, it is best to assess one’s POPs exposure levels by laboratory techniques using biological samples (e.g. blood). This creates two critical obstacles that have prevented the scientific community from investigating POPs-breast cancer link: (1) the extremely high cost of comprehensive laboratory measurement of POPs, and (2) limited availability of appropriate (i.e. obtained prior to breast cancer diagnosis) biological samples of breast cancer patients. In this IDEA application, we propose to investigate the association between blood levels of POPs and breast cancer risk by using an established biomarker for breast cancer risk - mammographic density (MD).
 
 
 
 
 
 
 
 
 
 On standard mammograms the dark area represents fat tissue, while light area represents breast tissue. The relative amount of the dense area on the mammogram, referred to as mammographic density (MD), is one of the strongest known predictors of breast cancer. MD can be determined on regular screening mammograms. By using this breast cancer biomarker, we can investigate the POPs-breast cancer link among women without breast cancer. 
 
 
 
 
 
 
 
 
 
 Our proposal avoids the cost-related obstacle by capitalizing on an ongoing CBCRP-funded study (#16ZB-8501; PI: Peggy Reynolds, co-investigator of this IDEA application), where blood POPs levels are comprehensively being measured and will be compared between breast cancer patients and control women sampled from the California Teachers Study (CTS) cohort. Second, our study design of using a breast cancer biomarker and conducting the study only among non-cases allows us to avoid the second obstacle stemming from the use of blood samples of breast cancer patients (i.e. that may be affected by being obtained after breast cancer diagnosis and treatment). 
 
 
 
 
 
 
 
 
 
 The question(s) or central hypotheses of the research: We hypothesize that serum POPs levels are positively associated with higher MD, which is a known predictor of increased breast cancer risk. 
 
 
 
 
 
 
 
 
 
 The general methodology: The study participants will be 160 postmenopausal women identified from the pool of ~1,100 participants without breast cancer in the “CTS POPs study” (#16ZB-8501), whose serum POPs levels are comprehensively being measured. From the participants in this proposed study, we will collect mammograms along with information on potential confounders. A highly experienced researcher will assess MD of the 160 women using a well validated computer-assisted tool. The association between POPs levels and MD will be investigated using linear regression analyses (i.e. a type of statistical methods) taking into account potential confounders. We will analyze the data using various advanced statistical techniques, evaluating each compound individually and as combinations considering a priori groupings by chemical classes, biological properties, and correlations (i.e. inter-relationships) between each compound. 
 
 
 
 
 
 
 
 
 
 Innovative elements of the project: To our knowledge, we are the first to investigate the association between a comprehensive list of POPs and breast cancer risk among women without breast cancer using an established biomarker of breast cancer risk. This study design is innovative in that this approach allows us to avoid the limitations of cost and timing of blood collection as discussed above. In particular, we are investigating a comprehensive list of POPs, not only the old but also the new POPs in relation to breast cancer risk. Considering that these newer POPs are widely detected in the US population, it is surprising that their breast carcinogenic potentials have rarely been investigated in human populations. Our study is innovative in that we are investigating this rarely-addressed but important area of breast cancer research.