Authors
Settimi L, Masina A, Andrion A, Axelson O.

Title
Prostate cancer and exposure to pesticides in agricultural settings.

Journal
International Journal of Cancer. 2003;104(4):458-61

Summary
The association between prostate cancer and occupation has been examined in several studies, with farming and agricultural-related occupations associated with an increased risk of the disease. However, studies have not been able to link exposure to a specific chemical or agent with increased risk of prostate cancer. The multitude of pesticides used in agriculture depend on crop type, geographical region, season, historical period and thus, the pattern of exposure to the worker may be quite variable. Here Settimi et al. investigate the association between prostate cancer and exposure to specific pesticides. Their initial statistical analysis, previously published, showed an increased risk of prostate cancer among farmers. Using the same subject pool, the authors have now focused efforts to specifically evaluate the exposure to specific pesticides.

The study design was a hospital-based, case-control study (Italy 1990-1992) examining the associations between 14 types of cancer in men, aged 20-75 years residing in 5 selected areas of Italy. Controls were selected for each cancer case series from among the other cancer cases. The current study used 124 prostate cancer cases and 659 cancer case controls (cancer of lip, oral cavity, oropharynx, stomach, colon, rectum, larynx, skin melanoma, skin non melanoma, bladder, kidney, non Hodgkin's lymphoma), aged 49-75 years. Questionnaires were used to obtain information on sociodemographic characteristics, employment history, smoking, alcohol consumption, family history of cancer and diet. Data on pesticide use, protective equipment and detailed information on specific agriculture tasks were obtained from subjects employed in agriculture. A team of agronomists identified specific pesticide use protocols and used national statistics on pesticide use, suppliers' records, personal recall of professional consultants and personal experience to determine the exposures to pesticides.

Agricultural occupations were associated with a 40% increased risk of prostate cancer (OR=1.4, 95% CI=0.9-2.0). Other occupations associated with an increased risk included food and tobacco production industries and chemical industries. The excess risk of prostate cancer for agricultural workers was related to pesticide use as reported by 71% farmers and workers (OR=1.5, 95% CI=1.0-2.4). Major components of pesticides associated with an increased risk of prostate cancer included organochlorines (OR=2.5, 95%CI=1.4-4.2), specifically DDT (OR=2.0, 95% CI=1.1-3.0) and combined treatments of dicofol and tetradifon (OR=2.8, 95% CI=1.5-5.0). Increased duration of exposure to dicofol and tetradifon, commonly used as acaricides since 1960's, was also associated with increased risk of prostate cancer (p<0.001).

This study is one of the few studies that examined the risk of prostate cancer with specific pesticide exposure. The strengths of this study include the study design (hospital-based, case-control) which would be expected to minimize interviewer and differential recall bias. This study used a cancer control group, comprised of cancer cases other than prostate cancer. It is possible that pesticide exposure could be carcinogenic in general, which would favour the null hypothesis (no increased risk in prostate cancer group vs. cancer controls). The use of an 'expert agronomist panel' to assess pesticide exposure is less accurate than serum or tissue levels obtained directly from study participants, but provides suggestive evidence that pesticide exposure may be involved in the pathobiology of prostate cancer.

Many organochlorine compounds have been suggested to cause disease or adverse effects through disruption of the endocrine system, however there is no evidence to support this mechanism of action for prostate cancer. Epidemiological studies and experimental data suggest that both DDT and difocal are carcinogens, and disrupt gap-junctional intercellular communication in both rodent and human cells. A DDT metabolite, o, p'-DDT, has been reported to induce proliferation of prostate cancer cells in vitro, however this area requires further investigation.

The major risk factors for prostate cancer are family history and race, with diet, occupation, lifestyle and other factors also associated with an increased risk. The association with specific pesticide components and prostate cancer seems promising, and is consistent with previous studies linking the agriculture industry with increased risk of prostate cancer. Further study is required to specifically examine pesticide exposure using direct tissue measurements in prostate cancer patients and to elucidate the mechanism of action of these chemicals.