From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action.

The objective of the present work is to critically summarize published studies and reassess the state of knowledge on a highly controversial topic: the potential association between prenatal exposure to passive smoking as well as maternal active smoking and postnatal exposure to environmental tobacco smoke (ETS) and enhanced incidence of childhood cancer. Elements to be considered include the substantial proportion of pregnant women who remain smokers, the widespread nature of exposure to ETS during pregnancy as well as during childhood, the known toxicology of tobacco smoke, and in particular sidestream smoke, characterized by a rich carcinogen content, the specific metabolism of foetuses and new-borns and finally the amount of epidemiologic data already available. We conducted a thorough review of the literature to identify studies either exclusively dealing with the effects of passive smoking on the occurrence of childhood cancers or more generally etiologic studies of cancer, be it overall or site-specific. We identified close to 50 publications presenting pertinent results from epidemiological investigations and about 50 more on mechanisms and metabolism, smoking in pregnancy and exposure to ETS as well as selected reviews and commentaries. Collaborative epidemiological studies were conducted in the United Kingdom (UK), USA, Sweden, Netherlands and internationally (France, Italy). In addition, other studies were also available from the USA, UK, Canada, Australia, Sweden, Italy, Denmark and People's Republic of China. The vast majority were case-control studies dealing with all cancers, leukaemia and lymphomas, central nervous system (CNS) tumours, Wilms' tumour, retinoblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, bone and soft tissues tumours, germ cell tumours, as well as specific histological types of leukaemias, lymphomas or CNS tumours. No strong association between maternal smoking in pregnancy and/or exposure to ETS and childhood cancer is found. Yet, several studies found slightly increased relative risks, generally smaller than 1.5, i.e. the order of magnitude associated with some recognized hazards of exposure to ETS (1.2 to 1.3 for adult lung cancer and cardiovascular diseases). Tumours most often found associated with maternal smoking in pregnancy or ETS exposure are childhood brain tumours and leukaemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies coupled with demonstration of genotoxic effects on the foetus of exposure to metabolites of tobacco smoke, and demonstrable presence of adducts should lead to strong recommendations aiming at fully protecting foetuses, new-borns and infants from tobacco smoke.