Pesticide and Gene Interactions in Latina Farm Workers

Institution: University of California, San Francisco
Investigator(s): Paul  Mills , Ph.D., MPH -
Award Cycle: 2008 (Cycle 14) Grant #: 14IB-0032 Award: $67,893
Award Type: IDEA
Research Priorities
Etiology>Environment and gene/environment interactions: nature vs. nurture



Initial Award Abstract (2008)
Susceptibility to cancer in humans is a function of both environmental factors (including chemical exposures) and constitutional factors (including genetics). Previous studies have suggested, though not proven, that organochlorine (OC) pesticides (which include the now-banned DDT) increase breast cancer risk; additionally common variants of certain genes such as the BRCA genes and carcinogen metabolizing genes may increase breast cancer risk. It is then possible that the genetic make-up of a woman may predispose her to adverse effects from chemical exposures and increase her risk for developing breast cancer.

We plan to assess breast cancer risk in a population of female Hispanics residing in rural central in California who have been heavily exposed to pesticides (including the OCs dieldrin, chlordane and heptachlor) by collecting detailed occupational histories, pesticide exposure information, and saliva (DNA) samples to test for variants in genes that may metabolize these pesticides. We plan to identify and analyze approximately 100 Hispanic females recently (2005-2006) diagnosed with breast cancer and 100 controls to evaluate the relationship between OC pesticide exposure, xenobiotic (i.e., a chemical which is found in a person, but which is not normally produced or expected to be present)-metabolizing genes (CYP1A1, CYP1A2, CYP1B1, GSTM1, GSTT1 and GSTP1), and their interaction on breast cancer risk. We will use a newly developed “Job Exposure Matrix” to assess current and historic pesticide use in the locations where these women have lived and worked. This will be used in the analysis to estimate lifetime exposure to OC pesticides.

The project data is designed to determine, (1) if breast cancer risk is increased among women living and working in areas heavily exposed to OC pesticides, (2) whether variants in pesticide metabolizing genes increase breast cancer risk, and (3) if there is an interaction between OC exposure and common variants of carcinogen metabolizing genes on breast cancer risk. This study is very innovative in that it combines the resources of several agencies in California: the California Cancer Registry (CCR), the Survey Research Group (SRG), Fresno State University, the University of California, San Francisco and the Department of Pesticide Regulation (DPR) in conducting novel breast cancer research. In addition, we propose to use new techniques for identifying important gene by environmental interactions in breast cancer causation.


Progress Report 1 (2009)
The overall scientific goal of our research project is to study the relationship of environmental chemical exposure, particularly exposure to the highly persistent endocrine disrupting organochlorines chemicals, to breast cancer risk, in a group of Hispanic female residents of California's San Joaquin Valley, the most intensively farmed area of the U.S. Additionally, we will evaluate whether genetic polymorphisms in CYP and GST genes are associated with modified breast cancer risk among pesticide exposed Hispanic women. It should be noted that this study is a feasibility study and we are gaining valuable experience and insights from our experience in this effort which can be applied in further research in this field.

In this first seven months of the study (Oct. 15, 2008-May 30, 2009) several aims were completed including:
1) We submitted request for Hispanic breast cancer cases to the CCR. This step was delayed until Institutional Review Board (IRB) approval was obtained from two IRBs (a requirement for obtaining cancer patient names and contact information from the CCR).
2) A methodology for selecting modified random digit dial controls was established with the Survey Research Group (SRG).
3) A modified survey instrument for use in this study, specifically adapted work history questions for smooth incorporation in the job exposure matrix is developed.
4) We developed a verbal consent script for the interview.
5) We developed two written consent forms (one for cases and one for controls) for participants providing a saliva sample.
6) We translated survey instrument, consent script and written consent forms from English to Spanish.
7) We gained IRB approval from two IRBs, namely the Regional Community Medical Canters IRB (which serves as the IRB for UCSF operations in Fresno) and the state of California Committee for the Protection of Human Subjects (CPHS) IRB.
8) We obtained a subcontract with SRG to complete recruitment, consent, interviews and saliva collection for this study.
9) We reviewed and modified the survey instrument to adapt work history questions for use in the job exposure matrix.
10) Further work toward this objective will occur after data collection is completed.

We plan to fully implement the data collection activities in the next twelve months, to analyze both the questionnaire data and the genotyping results and to prepare manuscripts for publication.