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Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

ABSTRACT: BACKGROUND:Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lectin-2 (MBL2) gene resulting in well-known functional changes in innate immunity. METHODS:Childhood secondhand smoke exposure and lung cancer risk was assessed among men and women in the ongoing National Cancer Institute-Maryland Lung Cancer (NCI-MD) study, which included 624 cases and 348 controls. Secondhand smoke history was collected via in-person interviews. DNA was used for genotyping the MBL2 gene. To replicate, we used an independent case-control study from Mayo Clinic consisting of 461 never smokers, made up of 172 cases and 289 controls. All statistical tests were two-sided. RESULTS:In the NCI-MD study, secondhand smoke exposure during childhood was associated with increased lung cancer risk among never smokers [odds ratio (OR), 2.25; 95% confidence interval (95% CI), 1.04-4.90]. This was confirmed in the Mayo study (OR, 1.47; 95% CI, 1.00-2.15). A functional MBL2 haplotype associated with high circulating levels of MBL and increased MBL2 activity was associated with increased lung cancer risk among those exposed to childhood secondhand smoke in both the NCI-MD and Mayo studies (OR, 2.52; 95% CI, 1.13-5.60, and OR, 2.78; 95% CI, 1.18-3.85, respectively). CONCLUSIONS:Secondhand smoke exposure during childhood is associated with increased lung cancer risk among never smokers, particularly among those possessing a haplotype corresponding to a known overactive complement pathway of the innate immune system.

SUBMITTER: Olivo-Marston SE

PROVIDER: S-EPMC2951599 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

Olivo-Marston Susan E SE Yang Ping P Mechanic Leah E LE Bowman Elise D ED Pine Sharon R SR Loffredo Christopher A CA Alberg Anthony J AJ Caporaso Neil N Shields Peter G PG Chanock Stephen S Wu Yanhong Y Jiang Ruoxiang R Cunningham Julie J Jen Jin J Harris Curtis C CC

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20091201 12

<h4>Background</h4>Exposure to secondhand smoke during adulthood has detrimental health effects, including increased lung cancer risk. Compared with adults, children may be more susceptible to secondhand smoke. This susceptibility may be exacerbated by alterations in inherited genetic variants of innate immunity genes. We hypothesized a positive association between childhood secondhand smoke exposure and lung cancer risk that would be modified by genetic polymorphisms in the mannose binding lect ...[more]

PMID: 19959685

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Project description:BackgroundPrior findings relating secondhand tobacco smoke (SHS) exposure and internalizing problems, characterized by heightened anxiety and depression symptoms, have been equivocal; effects of SHS on neurodevelopment may depend on the presence of other neurotoxicants. Early life stress (ELS) is a known risk factor for internalizing symptoms and is also often concurrent with SHS exposure. To date the interactive effects of ELS and SHS on children's internalizing symptoms are unknown. We hypothesize that children with higher exposure to both prenatal SHS and ELS will have the most internalizing symptoms during the preschool period and the slowest reductions in symptoms over time.MethodsThe present study leveraged a prospective, longitudinal birth cohort of 564 Black and Latinx mothers and their children, recruited between 1998 and 2006. Cotinine extracted from cord and maternal blood at birth served as a biomarker of prenatal SHS exposure. Parent-reported Child Behavior Checklist (CBCL) scores were examined at four timepoints between preschool and eleven years-old. ELS exposure was measured as a composite of six domains of maternal stress reported at child age five. Latent growth models examined associations between SHS, ELS, and their interaction term with trajectories of children's internalizing symptoms. In follow-up analyses, weighted quintile sum regression examined contributions of components of the ELS mixture to children's internalizing symptoms at each time point.ResultsELS interacted with SHS exposure such that higher levels of ELS and SHS exposure were associated with more internalizing symptoms during the preschool period (β = 0.14, p = 0.03). The interaction between ELS and SHS was also associated with a less negative rate of change in internalizing symptoms over time (β=-0.02, p = 0.01). Weighted quintile sum regression revealed significant contributions of maternal demoralization and other components of the stress mixture to children's internalizing problems at each age point (e.g., age 11 WQS β = 0.26, p < 0.01).ConclusionsOur results suggest that prior inconsistencies in studies of SHS on behavior may derive from unmeasured factors that also influence behavior and co-occur with exposure, specifically maternal stress during children's early life. Findings point to modifiable targets for personalized prevention.

Project description:ObjectivesMannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.MethodsWe conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (?7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.ResultsPatients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P?=?0.019 and P?=?0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83-196.37; P?=?0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19-29.57; P?=?0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12-63.39; P?=?0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03-4.26; P?=?0.040).ConclusionsThis is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.

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Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

Publications

Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.

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