A prospective study of phthalates, BPA, and breast cancer
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:There is accumulating evidence that the risk of breast cancer is influenced by exposure to endocrine disrupting chemicals, including phthalates (PHTHs) and bisphenol A (BPA) that are used in a wide array of manufacturing, food packaging, and other consumer products. Exposure is ubiquitous and continuous; urinary levels of these chemicals are found in over 90% of U.S. subjects that were tested. Direct data relevant to the role of PHTHs and BPA as a risk factor for breast cancer are limited to four small studies (2 had fewer than 100 women with breast cancer); three of which found higher levels of PHTHs or BPA in breast cancer patients than in control women without breast cancer. However, a main limitation is that these findings were based on measurements in urine/blood specimens that were collected after the diagnosis of breast cancer so that the temporal sequence of events cannot be determined. It is essential to determine whether exposures to PHTHs and BPA are associated with risk of breast cancer using biological specimens collected before diagnosis of breast cancer.
 
 
 
 Research question(s) or central hypotheses: In Aim 1, we will test the hypothesis that breast cancer risk is increased among women with a) high pre-diagnostic urinary levels of PHTHs, b) high pre-diagnostic urinary levels of BPA; and that c) breast cancer risk is highest among women with high levels of both PHTHs and BPA. To better understand how PHTHs and BPA influence risk of breast cancer, we will test in Aim 2 the hypothesis that urinary levels of these chemicals are associated with race/ethnicity, established risk factors for breast cancer (e.g., parity, age at menarche, age at natural menopause), and with blood levels of biomarkers that are associated with obesity and inflammation. In Aim 3, we will examine the associations between levels of PHTHs and BPA with genetic variation in the metabolism of these chemicals.
 
 
 General methodology: This proposed will be conducted by a highly experienced transdisciplinary team of investigators from the University of Southern California, the Cancer Prevention Institute of California, and the University of Hawaii. The prospective investigation will be conducted using the well-established Multiethnic Cohort (MEC) that was established in Hawaii and California in 1993-1996 consisting of over 200,000 participants. This study capitalizes on the use of existing data on demographics, health behaviors and lifestyles, biorepositories, and long-term follow-up of female participants. Using urine specimens that were collected from study participants before the diagnosis of breast cancer, in Aim 1 we will investigate whether these chemicals are associated with risk of breast cancer in 1,023 women with breast cancer and 1,023 control women without breast cancer, who will be similar in regards to age, race/ethnicity, urine donation, and study site. In Aim 2, we will correlate urinary PHTH and BPA data of 1,023 control women with already available blood biomarkers on obesity and inflammation as well as questionnaire data on breast cancer risk factors. In Aim 3, we will correlate urinary PHTH and BPA data of 2,046 women (1,023 cases, 1,023 controls) with largely already available genetic polymorphism data. Urinary PHTHs and BPA will be measured using established and highly sensitive methods that have been used in other cohort studies. 
 
 
 Innovative elements: Our study is highly innovative as: 1) it examines the study hypothesis using a large scale prospective study that includes five major U.S. racial/ethnic groups; 2) it investigates possible pathways by which PHTHs and BPA may influence breast cancer biology by integrating already collected questionnaire and biomarker data with PHTHs and BPA levels that will be measured in urine samples; 3) it aims to disentangle the association between race/ethnicity and breast cancer risk by evaluating the contribution of PHTHs and BPA to breast cancer development across populations; and 4) it provides new information on the influence of genetic polymorphisms in the metabolism of PHTHs and BPA. 
 
 
 Advocacy involvement and relevance to the human issues associated with breast cancer: Ms. Chingos, a long-term patient advocate, will take part in the monthly meetings with the study team. We anticipate in-depth quarterly meetings in which Ms Chingos will be asked to review specific materials related to study progress as well as guide the dissemination of study results.