title: 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.
authors: Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892-4258, USA.
authors: Susan E
authors: SE
authors: Olivo-Marston
authors: Ping
authors: P
authors: Yang
authors: Leah E
authors: LE
authors: Mechanic
authors: Elise D
authors: ED
authors: Bowman
authors: Sharon R
authors: SR
authors: Pine
authors: Christopher A
authors: CA
authors: Loffredo
authors: Anthony J
authors: AJ
authors: Alberg
authors: Neil
authors: N
authors: Caporaso
authors: Peter G
authors: PG
authors: Shields
authors: Stephen
authors: S
authors: Chanock
authors: Yanhong
authors: Y
authors: Wu
authors: Ruoxiang
authors: R
authors: Jiang
authors: Julie
authors: J
authors: Cunningham
authors: Jin
authors: J
authors: Jen
authors: Curtis C
authors: CC
authors: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D014028:Tobacco Smoke Pollution