| Title: | In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk and Lung Cancer Incidence and Mortality in Adulthood. |
| Journal: | American Journal of Respiratory and Critical Care Medicine |
| Published: | 9 Aug 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35943859/ |
| DOI: | https://doi.org/10.1164/rccm.202112-2758oc |
Publication 7069
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Abstract
RATIONALE: The individual effects of early-life tobacco smoke exposure and its interactions with genetic factors on lung cancer in adulthood remain unclear.OBJECTIVES: To investigate the associations between early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) and lung cancer incidence and mortality.
METHODS: A total of 432,831 participants from the UK Biobank study were included. We estimated the associations of in utero exposure to tobacco smoke, the age of smoking initiation and their interactions with PRSs with lung cancer incidence and mortality in adulthood using Cox proportional hazard models.
MEASUREMENTS AND MAIN RESULTS: Lung cancer incidence [hazard ratio (HR): 1.59, 95% confidence interval (CI), 1.44-1.76] increased among participants with in utero tobacco exposure. Multivariable-adjusted HRs (with 95% CIs) of lung cancer incidence for smoking initiation in adulthood, adolescence, and childhood (vs. never smokers) were 6.10 (5.25-7.09), 9.56 (8.31-11.00), and 15.15 (12.90-17.79) (Ptrend <0.001). Similar findings were observed in lung cancer mortality. Participants with high PRSs and in utero tobacco exposure (vs. low PRSs participants without in utero exposure) had HR of 2.35 for lung cancer incidence (95%CI, 1.97-2.80, Pinteraction=0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction=0.032). High PRSs with smoking initiation in childhood (vs. never smokers with low PRSs) had HR of 18.71 for incidence (95% CI, 14.21-24.63, Pinteraction=0.004) and 19.74 for mortality (95%CI, 14.98-26.01, Pinteraction=0.033).
CONCLUSIONS: In utero and childhood/adolescence exposure to tobacco smoke and its interaction with genetic factors may substantially increase the risks of lung cancer incidence and mortality in adulthood.
20 Authors
- Heng He
- Ming-Ming He
- Haoxue Wang
- Weihong Qiu
- Lei Liu
- Lu Long
- Qian Shen
- Shanshan Zhang
- Shifan Qin
- Zequn Lu
- Yimin Cai
- Ming Zhang
- Siyuan Niu
- Jiaoyuan Li
- Na Shen
- Ying Zhu
- Jianbo Tian
- Jiang Chang
- Xiaoping Miao
- Rong Zhong
Enabling scientific discoveries that improve human health