Early-life Tobacco Smoke Exposure Research Articles

Early-life tobacco smoke exposure and stroke risk: a prospective study of 341,783 and 352,737 UK Biobank participants.

Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging. This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition

IntroductionThe growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. ObjectivesThis study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. MethodsData on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. ResultsIndividuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: −0.51, −0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. ConclusionsOur findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Cancer Incidence in Adulthood: A Prospective Cohort Study

ObjectiveTo evaluate the association of early-life tobacco smoke exposure, especially interacting with cancer genetic variants, with adult cancer. Participants and MethodsWe examined the associations of in utero tobacco smoke exposure, age of smoking initiation, and their interaction with genetic risk levels with cancer incidence in 393,081 participants from the UK Biobank. Information on tobacco exposure was obtained by self-reported questionnaires. A cancer polygenic risk score was constructed by weighting and integrating 702 genome-wide association studies–identified risk variants. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for overall cancer and organ-specific cancer incidence. ResultsDuring 11.8 years of follow-up, 23,450 (5.97%) and 23,413 (6.03%) incident cancers were included in the analyses of in utero exposure and age of smoking initiation, respectively. The HR (95% CI) for incident cancer in participants with in utero exposure to tobacco smoke was 1.04 (1.01-1.07) for overall cancer, 1.59 (1.44-1.75) for respiratory cancer, and 1.09 (1.03-1.17) for gastrointestinal cancer. The relative risk of incident cancer increased with earlier smoking initiation (Ptrend<.001), with the HR (95% CI) of 1.44 (1.36-1.51) for overall cancer, 13.28 (11.39-15.48) for respiratory cancer, and 1.72 (1.54-1.91) for gastrointestinal cancer in smokers with initiation in childhood compared with never smokers. Importantly, a positive additive interaction between age of smoking initiation and genetic risk was observed for overall cancer (Padditive=.04) and respiratory cancer (Padditive=.003) incidence. ConclusionIn utero exposure and earlier smoking initiation are associated with overall and organ-specific cancer, and age of smoking initiation interaction with genetic risk is associated with respiratory cancer.

Early-life tobacco smoke exposure, genetic susceptibility and the risk of type 2 diabetes in adulthood: A large prospective cohort study

ObjectivesWe aimed to assess the relationships between early-life tobacco smoke exposures and the incident risk of type 2 diabetes (T2D) in later life as well as the joint effects and interactions between genetic susceptibility and early-life tobacco exposures. MethodsWe used data on in utero tobacco exposure and the age of smoking initiation to estimate the status of early-life tobacco exposure in the UK Biobank. Cox proportion hazard models were applied to estimate the associations between early-life tobacco exposure and T2D risk and investigate joint effects and interactions of early-life tobacco smoke exposure with genetic susceptibility. ResultsAmong 407,943 subjects from the UK Biobank, 17,115 incident cases were documented during a median follow-up of 12.80 years. Compared with subjects without prenatal tobacco exposure, those with in utero tobacco exposure had a higher risk of T2D with a hazard ratio (HR) (95 % confidence interval [CI]) of 1.11 (1.08, 1.15). Besides, the HRs (95 % CIs) of incident T2D for smoking initiation in adulthood, adolescence, and childhood (vs. never smokers) were 1.36 (1.31, 1.42), 1.44 (1.38, 1.50), and 1.78 (1.69, 1.88), respectively (P trend <0.001). No interaction between early-life tobacco exposure and genetic susceptibility was observed. In addition, participants with prenatal (HR 4.67 [95 % CI 4.31, 5.06]) or childhood (6.91 [6.18, 7.72]) tobacco exposure combined with high genetic risk showed the highest risk of T2D, compared to low genetic risk subjects without early-life smoke exposure. ConclusionEarly-life tobacco exposure was associated with an increased risk of T2D later in life regardless of genetic background. This highlights the significance of education campaigns aimed at reducing smoking among children, adolescents, and pregnant women as an effective measure to combat the T2D epidemic.

In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood.

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) (Ptrend < 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, Pinteraction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction = 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, 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.

Epigenetic Biomarkers of Prenatal Tobacco Smoke Exposure Are Associated with Gene Deletions in Childhood Acute Lymphoblastic Leukemia.

Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases. Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers. We found an association between DNA methylation at AHRR CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02-1.69] for each 0.1 β value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10-1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09-1.57). We provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL. Analyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.

Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families

BackgroundA positional cloning study of bronchial hyper-responsiveness (BHR) at the 17p11 locus in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families showed significant interaction between...

Tobacco control policies in relation to child health and perinatal health outcomes

The global epidemic of tobacco use continues to cause a considerable burden of premature death and disease.1 2 Worldwide, over 1 billion people are regular smokers, and the societal costs...

Correlates of Prenatal and Early-Life Tobacco Smoke Exposure and Frequency of Common Gene Deletions in Childhood Acute Lymphoblastic Leukemia.

Tobacco smoke exposure has been associated with risk of childhood acute lymphoblastic leukemia (ALL). Understanding the relationship between tobacco exposures and specific mutations may yield etiologic insights. We carried out a case-only analysis to explore whether prenatal and early-life tobacco smoke exposure influences the formation of leukemogenic genomic deletions. Somatic copy number of 8 genes frequently deleted in ALL (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) was assessed in 559 pretreatment tumor samples from the California Childhood Leukemia Study. Parent and child's passive tobacco exposure was assessed using interview-assisted questionnaires as well as DNA methylation in aryl-hydrocarbon receptor repressor (AHRR), a sentinel epigenetic biomarker of exposure to maternal smoking during pregnancy. Multivariable Poisson regressions were used to test the association between the smoking exposures and total number of deletions. Deletion burden varied by subtype, with a lower frequency in high-hyperdiploid and higher frequency in ETV6-RUNX1 fusion ALL. The total number of deletions per case was positively associated with tobacco smoke exposure, in particular for maternal ever-smoking (ratio of means, RM, 1.31; 95% CI, 1.08-1.59), maternal smoking during pregnancy (RM, 1.48; 95% CI, 1.12-1.94), and during breastfeeding (RM, 2.11; 95% CI, 1.48-3.02). The magnitude of association with maternal ever-smoking was stronger in male children compared with females (Pinteraction = 0.04). The total number of deletions was also associated with DNA methylation at the AHRR epigenetic biomarker (RM, 1.32; 95% CI, 1.02-1.69). Our results suggest that prenatal and early-life tobacco smoke exposure increase the frequency of somatic deletions in children who develop ALL. Cancer Res; 77(7); 1674-83. ©2017 AACR.

Early smoke exposure is associated with asthma and lung function deficits in adolescents

ABSTRACTObjective: Early life tobacco smoke exposure may influence asthma, lung function and lung function growth into adolescence. We aimed to determine the associations between perinatal smoke exposure and asthma and lung function up to 18 years of age. Methods: We prospectively recorded perinatal parental smoking and measured respiratory outcomes at 12 and 18 years in the Melbourne Atopy Cohort Study (MACS), a longitudinal birth cohort. Multiple logistic regression was used to analyse the associations between perinatal smoke exposure and asthma at 12 (n = 370) and 18 years (n = 411). Multiple linear regression was used to investigate the relationship between perinatal smoking and: lung function (12 and 18 years) and lung function growth (between 12 and 18 years). Results: At 18 years, girls exposed to parental smoking during the perinatal period had increased odds of asthma (OR: 3.45, 95%CI: 1.36, 8.77), reduced pre-bronchodilator Forced expiratory volume in one-second (FEV1) (−272 ml/s; −438, −107); FEV1/ forced vital capacity (FVC) (−0.038; −0.065, −0.010); mid expiratory flow (MEF25-75) (−430 ml/s; −798, −61), and reduced post-bronchodilator FEV1/FVC (−0.028, −0.053, −0.004). No associations were found for boys (pre-bronchodilator FEV1 26ml/s; −202, 255; FEV1/FVC 0.018; −0.013, 0.049). Conclusions: Perinatal smoke may affect risk of asthma, reduce lung function and lung function growth in adolescence. Girls appear to be more susceptible than boys.

Antenatal and early life tobacco smoke exposure in an African birth cohort study.

Exposure to tobacco smoke in African infants has not been well studied, despite the high burden of childhood respiratory disease in these communities. To investigate the prevalence of antenatal and early life tobacco smoke exposure and associations with infant birth outcomes in an African birth cohort, the Drakenstein Child Health Study. Self-report questionnaires assessing maternal and household smoking were administered. Maternal and infant urine cotinine testing was conducted antenatally, at birth and at 6-10 weeks of life to measure tobacco smoke exposure. Multivariate regression models explored the associations between exposure to smoke and infant birth outcomes. Of 789 pregnant women included, 250 (32%) were active smokers on cotinine testing. At birth and at 6-10 weeks of life, respectively 135/241 (56%) and 154/291 (53%) infants had urine cotinine levels indicating tobacco smoke exposure. Household smoking was prevalent and was associated with positive infant cotinine test results. Antenatal maternal smoking was associated with decreased infant birthweight-for-age Z-score (0.3, 95%CI 0.1-0.5). Antenatal and early life tobacco smoke exposure is highly prevalent in this community, and may impact on birth outcomes and subsequent child health. Smoking cessation interventions are urgently needed to reduce tobacco smoke exposure in African communities.

Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure

Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure

Effects of Tobacco Smoke Exposure in Childhood on Atopic Diseases

Although the smoking prevalence in the United States continues to decline since the Surgeon General's first report in 1964, certain vulnerable populations continue to be disproportionately affected by the adverse consequences of tobacco smoke exposure. Children are particularly vulnerable to exposure and are likely to suffer from both short- and long-term adverse consequences after early life tobacco smoke exposure. An overwhelming amount of evidence supports an association between asthma development and tobacco smoke exposure, and evidence is mounting that tobacco smoke exposure may also increase risk of IgE sensitization. This manuscript will review the effects of tobacco smoke exposure in childhood on the development of asthma and allergic sensitization, and will review practical strategies to assist motivated parents with smoking cessation.