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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk

Susan E. Olivo-Marston, Ping Yang, Leah E. Mechanic, Elise D. Bowman, Sharon R. Pine, Christopher A. Loffredo, Anthony J. Alberg, Neil Caporaso, Peter G. Shields, Stephen Chanock, Yanhong Wu, Ruoxiang Jiang, Julie Cunningham, Jin Jen and Curtis C. Harris
Susan E. Olivo-Marston
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Ping Yang
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Leah E. Mechanic
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Elise D. Bowman
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Sharon R. Pine
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Christopher A. Loffredo
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Anthony J. Alberg
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Neil Caporaso
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Peter G. Shields
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Stephen Chanock
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Yanhong Wu
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Ruoxiang Jiang
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Julie Cunningham
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Jin Jen
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Curtis C. Harris
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DOI: 10.1158/1055-9965.EPI-09-0986 Published December 2009
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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. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3375–83)

Keywords
  • Secondhand smoke
  • childhood
  • mannose binding lectin
  • innate immunity
  • lung cancer

Footnotes

  • Grant support: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research to [C. Harris], NIH grants [R03-77118, R01-80127 to P. Yang, R. Jiang, and J. Cunningham], and the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute to [S. Olivo-Marston].

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • ↵8http://snp500cancer.nci.nih.gov

    • Received September 24, 2009.
    • Revision received October 13, 2009.
    • Accepted October 14, 2009.
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Cancer Epidemiology Biomarkers & Prevention: 18 (12)
December 2009
Volume 18, Issue 12
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Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk
Susan E. Olivo-Marston, Ping Yang, Leah E. Mechanic, Elise D. Bowman, Sharon R. Pine, Christopher A. Loffredo, Anthony J. Alberg, Neil Caporaso, Peter G. Shields, Stephen Chanock, Yanhong Wu, Ruoxiang Jiang, Julie Cunningham, Jin Jen and Curtis C. Harris
Cancer Epidemiol Biomarkers Prev December 1 2009 (18) (12) 3375-3383; DOI: 10.1158/1055-9965.EPI-09-0986

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Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk
Susan E. Olivo-Marston, Ping Yang, Leah E. Mechanic, Elise D. Bowman, Sharon R. Pine, Christopher A. Loffredo, Anthony J. Alberg, Neil Caporaso, Peter G. Shields, Stephen Chanock, Yanhong Wu, Ruoxiang Jiang, Julie Cunningham, Jin Jen and Curtis C. Harris
Cancer Epidemiol Biomarkers Prev December 1 2009 (18) (12) 3375-3383; DOI: 10.1158/1055-9965.EPI-09-0986
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