Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer.

Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.

Coumaphos intoxications mimic food poisoning.

Reports of food poisoning caused by pesticide-contaminated food are rare in the medical literature. In this paper, we report six patients who suffered food poisoning in two separate episodes in which the pesticide coumaphos was apparently misused as a food flavoring. These six patients presented not only the general manifestations of gastroenteritis, but also some unusual extraintestinal symptoms. These included cholinergic overactivity (miosis, urinary incontinence and hypersalivation) that led us to suspect organophosphate intoxication. This diagnosis was confirmed by serial changes in RBC cholinesterase and pseudocholinesterase activity, and by the presence of coumaphos in the contaminated food. Of the six patients, one was dead on arrival. Another patient developed progressive respiratory failure and required mechanical ventilation. The mortality rate among our cases was 16.7%. Since the coumaphos was apparently added to food during cooking, its toxic effects do not appear to be mitigated by heating. When food poisoning cases present with both gastroenteritis and unusual autonomic symptoms, the autonomic syndromes will aid in the diagnosis and management of these critically ill patients.

Evaluation of hazards involved in treating cattle with pour-on organophosphate insecticides.

Eighteen veterinarians regularly practicing organophosphate pour-on treatment of cattle for grub infestations were examined in the course of the 1975-1976 application season for symptoms and signs as well as enzymologic and chemical evidence of organophosphate absorption. Some subjects reported headache, nausea, and irritation of the face and throat during chemical applications in poorly ventilated buildings. Organophosphate absorption was not sufficient to depress blood cholinesterase activities, and only occasionally generated measurable amounts of alkyl phosphate meatbolites in urine of exposed veterinarians.