Paternal preconception smoking increased risk for children under 5 years old for several common childhood cancers including acute lymphocytic leukemia (ALL), lymphoma, and brain cancer. Risk was highest for children whose fathers smoked heavily or for a long time.
"This is the first epidemiologic study to suggest that duration of smoking and number of cigarettes smoked per day increases the risk of childhood cancer," said lead author Bu-Tian Ji, M.D., of the National Cancer Institute (NCI) and Columbia University in New York. Ji's co-authors are from the Shanghai Cancer Institute, the Shanghai Xin-Hua Hospital, the University of Minnesota in Minneapolis, and NCI.
"An important feature of the study population was the wide range of smoking behavior by fathers and the almost complete absence of smoking among mothers," a common pattern in China, Ji said. "Thus, it was possible to assess independently the effects of paternal smoking in the absence of maternal smoking."
Most previous studies of childhood cancer have focused on maternal smoking. Of the few studies that have evaluated the effects of paternal smoking, most could neither disentangle the effects of paternal from maternal smoking nor evaluate the effects of smoking during different time periods, for example before conception and after birth. Some studies have reported finding associations between paternal smoking and a variety of childhood cancers, while others have reported finding no association.
Researchers in the United Kingdom published a study this year in the British Journal of Cancer showing a link between paternal, but not maternal smoking and cancer death among U.K. children from 1953 to 1955.
In the Shanghai study, the research team interviewed the fathers and mothers of 642 cancer patients less than 15 years old, and the parents of 642 Shanghai children without cancer who were matched to the children with cancer by age and sex and who served as a control group.
Parents were asked about a variety of behaviors and exposures potentially related to cancer risk. These included tobacco and alcohol use before and after conception, residential and occupational history, family history, and birth-related events.
Fathers who had ever smoked cigarettes were 30 percent more likely to have a child with cancer than fathers who had never smoked. Most of this increased risk appears related to smoking before the child's conception as opposed to after the child's birth. (Because maternal passive smoking during pregnancy was not considered a major risk factor when the study began, the researchers did not collect information about paternal smoking during the mother's pregnancy.)
Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had a 3.8 times higher risk for ALL, a 4.5 times higher risk for lymphoma, a 2.7 times higher risk for brain tumors, and a 1.7 times higher risk for all cancers combined. (A pack-year is a cumulative measure of smoking: One pack-year is equivalent to smoking a pack of cigarettes each day for a year.) The elevated risk was seen only in children diagnosed under age 5.
In the United States, cancer is diagnosed each year in about 14 of every 100,000 children under 15 years old, according to the most recent estimates. Childhood cancer rates in Shanghai are slightly lower than U.S. rates.
The study did not address the question of how paternal smoking might increase childhood cancer risk. One possible explanation is that smoking causes genetic damage to sperm cells. The sperm cell mutations would then become inborn cancer-causing mutations in the offspring. Studies on people, on animals, and in the test tube suggest that cigarette smoke can damage sperm. An alternative possibility is that the increased cancer risk is due to mothers' passive exposure to fathers' cigarette smoke, but the authors believe this explanation is less likely.
Because the findings by Ji and co-authors are suggestive but not conclusive, additional large-scale population studies are needed to confirm the association between paternal smoking and childhood cancer risk. If the association is confirmed, further laboratory studies would be needed to investigate the role of genetic or other mechanisms that may be responsible.
"Results from our study may indicate a preventive strategy for men to reduce cancer risk in their offspring," Ji said.
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