Authors
Engel, L.S., Hill, D.A., Hoppin, J.A., Lubin, J.H., Lynch, C.F., Pierce, J., Samanic, C., Sandler, D.P., Blair, A., and Alavanja, M.C.

Title:
Pesticide Use and Breast Cancer Risk Among Farmers' Wives in the Agricultural Health Study

Source:
American Journal of Epidemiology. 161: 121-135. 2005.

Summary:
The knowledge that certain pesticides have estrogenic properties has fueled several epidemiological studies investigating the role pesticides may play in breast cancer etiology. The majority of epidemiological evidence does not support a relationship between pesticide exposure and breast cancer risk, however, many of these investigations suffered from inadequate sample sizes and poor measures of exposure. In addition, the potential influence of different periods of exposure and the effect of mixtures remains unknown.

Engel et al. conducted a large prospective cohort study to examine breast cancer risk among wives of farmers in relation to the use of individual pesticides by women themselves or by their husbands. Participants consisted of the wives of private pesticide applicators from Iowa and North Carolina who were enrolled in the prospective Agricultural Health Study between 1993 and 1997. Exposure information was obtained through a self-administered questionnaire which included questions about the frequency and duration of mixing and applying pesticides, the number of years the participant had lived or worked on a farm, distance of the participants' house from fields where pesticides were applied and household pesticide use. Information was also gathered on a range of demographic, lifestyle, health and reproductive factors. The farmers completed a similar but more detailed questionnaire about pesticide use, including the duration and frequency of use of specific pesticides. This information was used as a measure of possible indirect pesticide exposure to their wives. Breast cancer cases were identified through population-based cancer registries and the national death index. A total of 30,454 women were included in the cohort and 309 incident cases of malignant breast cancer occurred between enrollment and December 31, 2000.

Risk ratios were calculated for individual pesticides controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval (CI): 0.74-1.62) for women who reported ever applying pesticides and 1.05 (95% CI: 0.89 - 1.24) for women who reported never applying pesticides. The authors did not find a significant association between measures of potential direct and indirect cumulative exposure to all pesticides combined and breast cancer risk. However, some significantly increased risks were observed among women whose husbands used insecticides. These included the organochlorine insecticides heptachlor (rate ratio (RR)=1.6, 95% CI: 1.1-2.4) and dieldrin (RR=2.0, 95% CI: 1.1-3.3). Similar patterns of increased risk only in relation to their husbands' use were observed for carbaryl (RR=1.4, 95% CI: 1.0-2.0), captan (RR=2.7, 95% CI: 1.7-4.3) and 2,4,5-trichlorophenoxypropionic acid (2,4,5, TP) (RR=2.0, 95% CI: 1.2-3.2). In analysis stratified by menopausal status, increased risks were observed for premenopausal women who indicated that they had used chlorpyrifos (RR=2.2, 95% CI: 1.0-4.9), dichlorovos (RR=2.3, 95% CI: 1.0-5.3), and terbufos (RR=2.6, 95% CI: 1.1-5.9), all three of these pesticides are organophosphates. All of the decreased risks associated with the women's use and the increased risks associated with the husbands' use were found among the postmenopausal women. There was evidence of exposure-response trends in relation to cumulative use of certain pesticides by the husbands. The rate ratios associated with low and high cumulative dieldrin use were 1.4 (95% CI: 0.6-3.5) and 3.2 (95% CI: 1.3-8.0) respectively. The corresponding estimates for 2,4,5, TP use were 1.5 (95% CI:0.7-3.5) and 4.7 (95% CI: 2.2-9.6).

The authors did not find an association between breast cancer risk and overall pesticide use, however elevated risks were found in relation to the use of several specific pesticides. This study had several strengths over previous epidemiological investigations. All exposure information was collected prior to disease ascertainment thereby reducing the chance of exposure misclassification. In addition, the large size of the cohort allowed the authors to collect information about the use of many individual pesticides as well as data on many potential confounding factors and effect modifiers. Despite these strengths, several limitations must be considered. Due to the large number of pesticide exposures investigated, some associations are likely to have occurred by chance. This may explain why many of the results were inconsistent between geographic regions, and between the wives' and husbands' use. Another limitation is that the data used to assess pesticide-specific exposure-response relations were available only for the husbands' use. These exposures may have been inaccurate for some participants as there was no information about how long each woman had been married to her current partner. Therefore, although overall pesticide use does not appear to be associated with an increased rate of breast cancer in this cohort, use of certain pesticides may be related to increased risk. Further epidemiological studies which include additional occupational and lifestyle information are needed to explore the relation of exposure to these specific pesticides with the risk of breast cancer.