Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers

Background: Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. Purpose: We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. Methods: We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients (<15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. Results and Conclusions: Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7(95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. Implications: Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor.