Lessons learned from epidemiologic studies of environmental exposure and genetic disease

The induction of germ cell mutations with ionizing radiation and chemicals has been clearly demonstrated in experimental animal test systems. Less is known about the effects of environmental and other exposures on human germ cells. Epidemiologic studies of atomic bomb and childhood cancer survivors and their offspring have generally not indicated an excess risk for a variety of adverse reproductive outcomes and childhood diseases, including those due to germ cell mutations. Other epidemiologic studies, including the investigation of cancer among the offspring of fathers employed at the Sellafield nuclear facility in Great Britain and studies of paternal occupation and birth defects, have found associations. This paper reviews these studies and the methodologic problems inherent in the epidemiologic approach to evaluating environmentally induced germ cell mutagenesis in humans. Epidemiologic studies incorporating newly developed techniques for the detection of mutations and abnormalities in sperm may provide the sensitivity needed to determine precisely the magnitude of risk.