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    Research Grants Awarded

    Pesticide-Gene Interactions and Breast Cancer in Hispanic Farm Workers

    Study Section:
    Breast Cancer Disparities

    Scientific Abstract:
    a. Background: The relationship of organochlorine (OC) pesticides and xenobiotic-metabolizing genes on breast cancer risk is equivocal. Previous laboratory and epidemiologic research suggests that exposure to certain OCs, such as polychlorinated bi-phenyls (PCB) and OC pesticides (e.g. DDT) increases breast cancer risk. These chemicals are highly persistent in the environment, are lipophilic and may be endocrine disruptors (i.e. enhance or inhibit hormone synthesis). In addition, susceptibility to OC exposure may vary by polymorphic genes that may metabolize OC chemicals. Two gene families in the xenobiotic-metabolism pathway, cytochromes P450 (CYP) and glutathione S-transferases (GST), have received attention in this regard but their relationship to breast cancer is not fully understood. Identifying interactions between OC pesticides and CYP and/or GST polymorphisms on risk of breast cancer is of particular importance for women in agricultural occupations with heavy exposures to OC pesticides. The population to be served in this study consists of Hispanic farm working women in California who are heavily exposed to pesticides and, by definition, are poor, rural dwelling and thus far understudied with regards to breast cancer risk. b. Objective/Hypothesis. To assess the feasibility of conducting a large case-control study of OC exposure and CYP and GST polymorphisms in a population of current and former Hispanic female farm workers. c. Specific Aims. Working with our community partner (the Robert F. Kennedy Medical Plan of the United Farm Workers of America), we will interview and obtain saliva samples for approximately 100 Hispanic female farm workers diagnosed with breast cancer and 100 controls and evaluate the relationship between OC pesticide exposure, xenobiotic-metabolizing genes (CYP1A1, CYP1B1, GSTM1, GSTT1 and GSTP1), and their interaction on breast cancer risk. d. Study Design. An epidemiologic case-control study of breast cancer nested within a cohort of female farm workers is our study design. Data collection will be accomplished by telephone interview and saliva specimen collection. Questionnaire data will be used to construct a Job Exposure Matrix (JEM) to measure OC pesticide exposure and DNA will be extracted from saliva for genotyping of the CYP/GST genes. e. Potential Outcomes and Benefits of the Research. The benefits of the proposed research not only include adding to the current knowledge on the relationship between OC pesticides and breast cancer risk and CYP/GST gene polymorphisms and breast cancer risk but also gaining knowledge on the gene-environment interactions between these exposures. To our knowledge, this would be one of only two or three studies to investigate these interactions.

    Lay Abstract:
    Susceptibility to cancer in humans is a function of both environmental factors (including chemical exposures) and constitutional factors (including genetics). Breast cancer may exemplify this combination of factors. 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. Working with our community partner (the Robert F. Kennedy Medical Plan of the United Farm Workers of America), in this research, we plan to assess breast cancer risk in a population of female Hispanic farm workers 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 samples to test for variants in genes that may metabolize these pesticides. The resulting data will be tested to determine if breast cancer risk is increased among women heavily exposed to OC pesticides, to determine if variants in pesticide metabolizing genes increase breast cancer risk and, finally, to determine if there is an interaction between OC exposure and common variants of carcinogen metabolizing genes on breast cancer risk. This population makes an ideal group for implementation of the Komen Foundation Breast Cancer Disparities Research program.