Environmental Causes of Breast Cancer Across Generations

Institution: Public Health Institute
Investigator(s): Barbara  Cohn , Ph.D., MPH, MCP - Barbara  Cohn , Ph.D., MPH, MCP -
Award Cycle: 2009 (Cycle 15) Grant #: 15ZB-0186 Award: $1,327,947
Award Type: SRI Program Directed Awards
Research Priorities
Etiology and Prevention>Prevention and Risk Reduction: ending the danger of breast cancer

This is a collaboration with: 15ZB-0186A -

Initial Award Abstract (2009)

This study will test the idea that prenatal exposure to environmental chemicals increases the risk of breast cancer. Many of these compounds are known to affect fertility, birth outcomes and immune function and are thus suspected causes of or contributors to breast cancer. However, no human study has been able to measure exposure in the womb, a time of vulnerability for the developing fetus.

This project will focus on polycholorinated biphenyls (PCBs) and the chemical that it breaks down into in the body, which is known to increase estrogen action and to cross over to the fetus more readily than the original PCB compounds. Investigators will also further examine the insecticide DDT, which they previously linked to increased breast cancer risk.

This project will follow-up on the Child Health and Development Studies cohort, a group of women who gave birth in the Bay Area between 1959 and 1967. Daughters of these women will be surveyed to identify their risk factors and environmental exposures. Blood samples from when their mothers were pregnant will be tested for the suspect chemicals to look for differences between those women with a breast cancer diagnosis and those without in their 40s, and between women of different race/ethnicity, education and geographic areas.

CHDS granddaughters, who are now in young childhood and adolescence, when contemporary exposures to environmental chemicals can be captured at a vulnerable period of breast development, will also be invited to participate with their mothers.

This project will also establish procedures for ongoing participant involvement in this project as the daughters and the granddaughters move through the ages of breast cancer risk. An Advisory Committee consisting of cohort members will help design study procedures, materials, review research objectives and disseminate findings.

This project will result in a wholly unique three-generation study of the environmental causes of breast cancer and will describe disparities in these exposures based on multiple available classifications of social educational and geographic characteristics in addition to race/ethnicity. This project is the first “womb to breast cancer study”. Because prior research strongly implicates early life exposures as important, we expect to make a significant contribution to understanding preventable, environmental causes of breast cancer.

Final Report (2016)

The purpose of Three Generations of Breast Cancer Study (3Gs) is to examine whether exposure to environmental chemicals, such as pesticides, household cleaners, and industrial pollutants, before birth influences breast cancer risk. For this study, we recruited second-generation women from the Child Health and Development Studies, a cohort study launched in 1959, which now includes over 15,000 families. The second-generation participants were first enrolled in the CHDS when their mother was pregnant with them. Mothers provided a health interview and blood samples during pregnancy and the families have been followed for cancer status since the inception of the study. The aims of the 3Gs study include 1) Learn whether fetal exposure to environmental chemicals predicts breast cancer; 2) Re-enroll the second generation (CHDS daughters) and for the first time, recruit third generation females (CHDS granddaughters) to collect blood, urine and saliva samples and health information; and 3) Describe disparities in exposures by race and generation. We completed data collection by enrolling 3286 women in the telephone interview and 1194 in-person visits to collect bio-specimens, exceeding our goal of 955 in-person visits. For the 1194 in-person visits completed, 641 granddaughters participated, a higher proportion than estimated. Additionally, 494 participants enrolled in the PEDIGREE Study (94 more than the target), a 5-year study funded by the National Institutes of Health, which adds a mammogram collection and measurement of genetic changes to the in-person visit for a subset of second generation 3Gs participants. Biospecimen assays for environmental chemicals were completed in the lab of Dr. Myrto Petreas. The CRC funding we received in 2013 to provide individual-level results of these environmental chemicals to 3Gs participants will complete report-back and interviews in early 2016. Analysis of the relationship between in-utero exposure to DDT and breast cancer revealed that maternal o,p’-DDT predicted daughters’ breast cancer. Mothers’ lipids, weight, race, age, and breast cancer history did not explain the findings which were published in JCEM in 2015. Data analysis also revealed that generational differences in PFC levels are consistent with manufacturing changes over time and that PFC levels are higher among non-African Americans in both generations. Data analysis has identified disparities in other chemical levels in both generations; African Americans have higher levels of organochlorine pesticides and PCBs in both generations. Metabolomics analysis revealed metabolic pathways associated with DDT and PCBs and potential pathways to breast cancer. The CHDS will continue to interrogate these data to increase our understanding of the relationship between these early life environmental exposures and later health effects. This is the beginning of establishing the cohort as an important resource for breast cancer research on environmental exposures during critical developmental windows.

DDT Exposure in Utero and Breast Cancer
Prenatal DDT Exposure Tied to Nearly Four-fold Increase in Breast Cancer Risk

Symposium Abstract (2016)