Introduction

1. In 2004 the committee published a statement on prostate cancer, in which we discussed the known and potential risk factors associated with this disease. The statement included an evaluation of the epidemiological and other data on occupational groups and chemical exposures for which an association with prostate cancer has been proposed. Two occupational groups were considered: rubber workers, for whom we concluded that there was no convincing evidence of an increased risk of prostate cancer, and farmers/farm workers/pesticide applicators. In the case of this latter group, we concluded:

"…that there was some limited evidence to suggest an association between farmers/farm workers, exposure to pesticides and increased risk of prostate cancer. The possibility of such an association being causal could not be discounted and the published literature should continue to be monitored for further studies. The committee commented on the need for improved measures of exposure to pesticides and in particular herbicides. It was considered that the potential association between herbicide use by farmers and farm workers should be kept under review" (COC, 2004)

2. Recently, we were asked by the Pesticides Safety Directorate of the Department of the Environment, Food and Rural Affairs (Defra) to consider a report commissioned from the Institute of Occupational Medicine (IOM) entitled "Desk Study on Prostate Cancer and Pesticide Exposure"(IOM, 2006) and to advise on whether the report alters the conclusion of our 2004 statement. At the same time, we considered a newly published review and meta-analysis of cohort studies of prostate cancer risk in pesticide manufacturing workers (Van Maele-Fabry et al, 2006). We report here on our conclusions.

3. The IOM report is a narrative review of the epidemiology of occupational exposure to pesticides and the risk of prostate cancer, and of the potential mechanisms that might underlie any association. The report concludes that epidemiological studies of manufacturing workers exposed to pesticides have not reported an excess risk of prostate cancer. It also concludes that there are a large number of studies of agricultural workers exposed to pesticides but that, nevertheless, the results have been inconsistent: many have been negative or inconclusive, with a few showing positive results. We note that the report proposes that pesticides might cause prostate cancer through a potential endocrine-disrupting mechanism based on androgen imbalance. This proposal may be derived from data that suggest that low dose exposure to certain chemicals may lead to an increase in prostate gland weight in young mice (vom Saal et al, 1997) but these data are disputed by others (Ashby J et al, 1999) who were unable to reproduce these observations. Moreover, pesticides are not a generic group of chemicals but comprise compounds of different structures and biological activities. It is unlikely, therefore, that a single mechanism of action would apply to all pesticides.

4. The meta-analysis by Van Maele-Fabry et al (2006) was conducted on 16 studies of workers ever employed in pesticide manufacturing and with potential exposure to pesticides. The analysis combined relative risk estimates from both incidence and mortality studies to derive an overall meta-rate ratio of 1.28 (95% CI 1.05 -1.58). After grouping the data into specific chemical classes of pesticide, increased pooled rate ratios were reported for each class but statistically significant results were only reported for phenoxy herbicides contaminated with polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans. We note that there are some unresolved methodological issues in this analysis, for example, adjustment for confounding might have been unsatisfactory, as little is known about the risk factors for prostate cancer.

5. We consider that the individual studies to date of exposure to pesticides in farmers/farmworkers and in pesticide manufacturing workers provide no consistent support for an association with prostate cancer. A recent meta-analysis by Van Maele-Fabry et al (2006) provides some limited evidence of a weak association between pesticide exposure in manufacturing workers and prostate cancer. It is not uncommon that the more formal approach of meta-analysis differs in its conclusions from a narrative review based on individual papers. Causality cannot be inferred from the available data. We recommend that the literature on this topic is kept under review.

March 2007

COC/07/S1

References

Ashby J. Tinwell H and Haseman J (1999). Lack of effects for low dose levels of bisphenol A and diethylstilbestrol on the prostate gland of CF1 mice exposed in utero. Regulatory Toxicology and Pharmacology. 30(2 Pt 1), 156-66.

Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment. Prostate Cancer. Statement COC/04/S6 - December 2004. (http://www.advisorybodies.doh.gov.uk/coc/prostate.htm)

Institute of Occupational Medicine. Desk study on prostate cancer and pesticide exposure. Research project final report to Defra, 28 February 2006. (http://www.defra.gov.uk/science/project_data/DocumentLibrary/PS2609/PS2609_3823_FRP.doc)

Van Maele-Fabry G, Libotte V, Willems J and Lison D (2006). Review and meta-analysis of risk estimates for prostate cancer in pesticide manufacturing workers. Cancer Causes Control 17, 353-373.

vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Parmingiani S and Welshons WV (1997). Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci U S A 94(5), 2056-2061.

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