Mutagenic lifestyles? A review of evidence of associations between germ-cell mutations in humans and smoking, alcohol consumption and use of 'recreational' drugs.

In humans, associations between germ-cell mutations and hypothetical aetiological factors can be investigated by (1) examining the relationship between the factor of interest and conditions known to be of genetic aetiology; (2) examining the relationship between conditions of unknown aetiology and route of exposure, especially paternal preconceptional exposure. As regards smoking, alcohol and 'recreational' drugs, the first approach has been applied in studies of retinoblastoma, Wilms' tumour and chromosomal anomalies. Only Down's syndrome has received intensive investigation, in relation to maternal smoking during pregnancy; the relative risks would be compatible with there being no association in all recognized conceptuses. The second approach has been applied in studies of sperm quality, miscarriage, congenital anomalies and childhood cancer. The available studies do not show a consistent relationship between smoking and sperm quality; there are few data on the effects of the other exposures. There are a substantial number of studies of childhood cancer and smoking by the father; the majority do not indicate any relationship. Some studies of childhood cancer suggest a positive association with use of 'recreational' drugs by the parents, but it has not been possible to clarify which route of exposure, or the specific type of drug which may be involved. Use of molecular techniques to detect individual genetic changes should enable progress to be made in elucidating the origin of mutation. In the meantime, public health actions are justified on the basis of the known non-genetic effects of these agents.