Background: An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult. Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.

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Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted.

In a retrospective cohort study of 47 Wilms' tumor survivors and their 77 sibling controls, female survivors had a fourfold excess risk (risk ratio, 4.1; 95% confidence interval, 1.7-10.1) for any adverse livebirth outcome, including birth defects, compared with their sibling controls. Wives of male survivors had no apparent excess risk for problem pregnancies. The families had a number of severe reproductive problems and major birth defects, such as primary amenorrhea in two survivors, bicornuate uterus in two survivors and one control, and mental retardation in one male survivor and a male control. The son of a female survivor died after bilateral Wilms' tumors. Birth defects in the offspring of female survivors are compatible either with intrauterine constraint, possibly due to radiation-induced fibrosis or with the complex of malformations associated with Wilms' tumor. Female survivors of Wilms' tumor appear to be at increased risk for a variety of reproductive problems, from sterility to fetal loss, early delivery, and birth defects in offspring. Furthermore, relatives of survivors of Wilms' tumor may be at risk of having associated birth defects, with clinically significant consequences.