In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood
In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood
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DOI：
10.1164/rccm.202112-2758oc
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发表时间：
2023-01-15
影响因子：
24.7
通讯作者：
Zhong, Rong
中科院分区：
文献类型：
--
作者：
He, Heng;He, Ming-Ming;Zhong, Rong
基本原理：个体影响的早期生活烟草烟雾暴露及其相互作用与遗传因素对肺癌在adulted.Objectives：探讨早期生活烟草暴露的关联，以及他们的相互作用与多基因风险评分（PRS）与肺癌发病率和mortality.Methods：共432，831名参与者从英国生物银行研究。我们使用考克斯比例风险模型（proportional hazardsmodels. Measures）和主要结果估计了子宫内暴露于烟草烟雾、开始吸烟的年龄及其与PRS的相互作用与肺癌发病率和成年期死亡率的相关性：在子宫内暴露于烟草的参与者中，肺癌发病率（风险比[HR]：1.59，95%置信区间[CI]：1.44-1.76）增加。在成年、青少年和儿童期开始吸烟的肺癌发病率的多变量校正HR（95%CI）（与从不吸烟者相比）分别为6.10（5.25-7.09）、9.56（8.31-11.00）和15.15（12.90-17.79）（P趋势< 0.001）。在肺癌死亡率中也观察到类似的结果。高PRS和子宫内烟草暴露的受试者（与低PRS且无子宫内暴露的受试者相比）肺癌发病率的HR为2.35（95% CI，1.97-2.80，P-相互作用= 0.089），死亡率的HR为2.43（95% CI，2.05-2.88，P-相互作用= 0.032）。儿童期开始吸烟的高PRS（与PRS较低的从不吸烟者相比）发生率的HR为18.71（95% CI，14.21-24.63，P-相互作用= 0.004）和19.74（死亡率）（95% CI，14.98-26.01，P-相互作用= 0.033）。在子宫和童年/青少年暴露于烟草烟雾及其与遗传因素的相互作用可能会大大增加肺癌发病率和死亡率的风险，成年
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 of early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) with 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 (versus never-smokers) were 6.10 (5.25-7.09), 9.56 (8.31-11.00), and 15.15 (12.90-17.79) (P-trend < 0.001). Similar findings were observed in lung cancer mortality. Participants with high PRSs and in utero tobacco exposure (versus low PRSs participants without in utero exposure) had an HR of 2.35 for lung cancer incidence (95% CI, 1.97-2.80, P-interaction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, P-interaction= 0.032). High PRSs with smoking initiation in childhood (versus never-smokers with low PRSs) had HRs of 18.71 for incidence (95% CI, 14.21-24.63, P-interaction = 0.004) and 19.74 for mortality (95% CI, 14.98-26.01, P-interaction = 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.