Early Life Exposure to Tobacco Smoke and Lung Cancer in Adulthood

To the Editor:

A significant and well-constructed United Kingdom Biobank prospective cohort study named “In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood” was recently published in the Journal (1). He and colleagues have clearly identified that exposure to tobacco smoke in early life, with careful and quantifiable consideration of lung polygenic cancer risk via genome-wide association studies, was significantly associated with risks of lung cancer incidence and mortality in adulthood (1). This manuscript undoubtedly provides important information on lung cancer prevention in people’s early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents. And we want to take this opportunity to share some additional thoughts about this elaborate work.

First, as the authors declared in Methods and study limitations, the definition of early life tobacco exposure was self-reported and retrospectively collected after a long period of time in which recall bias seemed to be huge and inevitable. To reduce this kind of bias, we suggested the authors could perhaps consider using measurable biomarkers, like serum cotinine, to define tobacco smoke exposure, that was more precise and stable (2). And defining smoking exposure via serum cotinine made it possible to not only distinguish secondhand smoke and active smoke but also quantify the amount of tobacco smoke exposure to assess its dose–dependent relationship with lung cancer incidence and mortality (3). If serum cotinine was not available in this cohort, the authors could also take the smoking status of the father during the children’s early life into consideration because the impact of active smoke and secondhand smoke on cancer might not be the same.

Furthermore, we thought the mechanism behind the impact of early life tobacco smoke exposure on lung cancer development merited further discussion. Though not fully understood, untimely telomere length reduction could play an unfavorable role in cancer development. Whiteman and colleagues reported that maternal smoking during pregnancy was associated with shortened fetal telomere length, leading to early intrauterine programming for accelerated aging (4). Another HELIX (Human Early Life Exposome) cohort study revealed that both active smoke and secondhand smoke during pregnancy could accelerate telomere shortening in children (5), which might be strong risk factors for lung cancer risk and mortality. And many researchers showed that tobacco smoke induced abnormal oxidative stress followed by DNA breakage, resulting in the reduction of telomere length (6). Oxidative stress, characterized as excessive exogenous and endogenous reactive oxygen species aggregation, could lead to rapid and even specific telomeric DNA damage while inhibiting protective DNA damage response and hampering DNA repair (6). Impaired telomeres could also lead to mitochondrial dysfunction via activating tumor repressor gene p53 to promote oxidative stress (6). At the same time, oxidative stress-induced inflammation with elevated inflammatory cytokines such as IL-6 and TNFα (tumor necrosis factor α) could further aggravate the telomere-shortening process and cell injury (6).

In conclusion, this work obtaining data from a prospective United Kingdom Biobank cohort illustrated a strong negative effect of early year tobacco smoke exposure on lung cancer incidence and mortality in adulthood very well, raising public attention on tobacco control from an early life stage. We thank and congratulate the authors again for their elaborate and illuminating paper.