Early-life exposure to tobacco raises risk for lung cancer, mortality in adulthood
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Being exposed to tobacco in utero and in childhood/adolescence was linked to higher risks for lung cancer incidence and death later in life, according to study results published in American Journal of Respiratory and Critical Care Medicine.
Further, genetic factors appeared to amplify these associations, according to researchers.
“We observed that smoking exposure in the early life stages, including the prenatal period, childhood and adolescence, could strongly contribute to lung cancer incidence and mortality in adulthood,” Heng He, of the department of epidemiology and biostatistics and ministry of education key lab of environment and health at Tongji Medical College in Wuhan, China, and colleagues wrote. “The overall risk of lung cancer incidence and mortality increased as both genetic risk and the risk of in utero and childhood/adolescence tobacco exposure increased, in an exposure-response manner. Furthermore, the age of smoking initiation was also observed to interact with genetic factors to significantly increase the risks of lung cancer incidence and mortality.”
In a large prospective cohort study, He and colleagues analyzed 2006 to 2010 data from the UK Biobank to find associations between in utero tobacco exposure and lung cancer incidence (n = 393,081) and mortality (n = 432,831), as well as between age of smoking initiation and lung cancer incidence (n = 388,211) and mortality (n = 427,543), using Cox proportional hazard models.
In addition, researchers looked at how these early-life exposures interacted with genetic risk based on polygenic risk scores (PRSs) using 18 genetic variants associated with lung cancer among Europeans from the International Lung Cancer Consortium.
In utero exposure, smoking age
Median follow-up was 8.87 years.
Within the in utero exposure cohort, researchers observed 1,718 incident lung cancers and 1,750 deaths.
Researchers found a greater risk for lung cancer (HR = 1.59; 95% CI, 1.44-1.76) and death of lung cancer (HR = 1.7; 95% CI, 1.54-1.87) among those exposed to tobacco in utero than those without such exposure.
In the age of smoking initiation cohort, researchers observed 1,866 incident lung cancers and 1,916 deaths. Compared with never smokers, those who started smoking had higher multivariable-adjusted hazard ratios for lung cancer incidence, with the highest risk observed in childhood smoking (childhood HR = 15.15; 95% CI, 12.9-17.79; adolescence HR = 9.56; 95% CI, 8.31-11; adulthood HR = 6.1; 95% CI, 5.25-7.09).
Similarly, those who started smoking in childhood had a greater risk for death due to lung cancer (HR = 18.39; 95% CI, 15.63-21.65) compared with never smokers, with risks also observed but to a lesser degree for those who started smoking in adolescence (HR = 11.11; 95% CI, 9.61-12.85) and adulthood (HR = 7.98; 95% CI, 6.86-9.28).
Researchers additionally found that those exposed to tobacco in utero who started smoking as a child had increased risks for both lung cancer incidence (HR = 17.41; 95% CI, 13.89-21.82) and death (HR = 20.87; 95% CI, 16.64-26.17) than never smokers who did not experience tobacco exposure in utero.
Genetic risk, implications
Researchers found a higher risk for both studied lung cancer outcomes among those with high PRSs.
Specifically, results showed an increased risk for both lung cancer incidence (HR = 2.35; 95% CI, 1.97-2.8) and death (HR = 2.43; 95% CI, 2.05-2.88) among those with high PRSs and exposure to tobacco in utero vs. those with low PRSs and no in utero exposure.
Those with high PRSs who started smoking as a child had even greater risks for lung cancer (HR = 18.71; 95% CI, 14.21-24.63) and death of lung cancer (HR = 19.74; 95% CI, 14.98-26.01).
The risk for lung cancer incidence and mortality increased further when researchers accounted for in utero exposure, childhood smoking and high PRSs compared with no in utero exposure, no smoking and low PRSs (incidence HR = 24.6; 95% CI, 16.89-35.82; mortality HR = 23.35; 95% CI, 16.16-33.73).
Researchers additionally assessed population-attributable risks (PARs) for both outcomes and found that 14.5% of lung cancer incidence and 16.1% of lung cancer mortality could be avoided with no exposure to tobacco in utero.
Child/adolescent smokers contributed to 31% of the PAR for lung cancer incidence and 25.1% of the PAR for lung cancer death, according to researchers.
“The present study emphasized the important role of early-life factors that contribute to a person’s cancer risk later in life, suggesting that opportunities should be taken for preventing cancer from the beginning as early as the prenatal period and throughout childhood and adolescence, especially for individuals with high PRSs,” He and colleagues wrote. “Future studies need to further collect detailed early-life exposure information to clarify the important effects of early-life exposure on adulthood and the underlying genetic mechanisms.”
This study by He and colleagues adds to the literature indicating that more attention should be drawn on preventing lung diseases early in life, such as in the developmental stage, rather than just in adulthood, according to an accompanying editorial by Andrew Bush, MB, BS, MA, MD, professor of pediatrics and pediatric respirology at Imperial College in London and consultant pediatric chest physician at Royal Brompton Hospital.
“Urgent political action is needed across the globe to tackle childhood poverty, exposures to tobacco and pollutants, and reduction of respiratory tract infection by immunization, including in high-income countries,” Bush wrote. “The increased vulnerability of young people to the effects of tobacco also underscores the need to protect them from the as yet unquantifiable risks of e-cigarette use, in which context, the recent actions of the Federal Drug Administration banning a popular brand for marketing to children are particularly welcome and the judgment of the U.S. Court of Appeals for the District of Columbia Circuit particularly damaging.”