Childhood Exposure to Secondhand Smoke and Functional Mannose Binding Lectin Polymorphisms Are Associated with Increased Lung Cancer Risk

被引：42

作者：

Olivo-Marston, Susan E. ^{[1
,2
]}

Yang, Ping ^{[4
]}

Mechanic, Leah E. ^{[1
]}

Bowman, Elise D. ^{[1
]}

Pine, Sharon R. ^{[1
]}

Loffredo, Christopher A. ^{[6
]}

Alberg, Anthony J. ^{[7
]}

Caporaso, Neil ^{[3
]}

Shields, Peter G. ^{[6
]}

Chanock, Stephen ^{[3
]}

Wu, Yanhong ^{[4
]}

Jiang, Ruoxiang ^{[4
]}

Cunningham, Julie ^{[4
]}

Jen, Jin ^{[5
]}

Harris, Curtis C. ^{[1
]}

机构：

[1] NCI, Human Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA

[2] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div,NIH, Bethesda, MD 20892 USA

[3] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[4] Mayo Clin, Div Epidemiol, Rochester, MN USA

[5] Mayo Clin, Adv Genome Technol Ctr, Rochester, MN USA

[6] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA

[7] Med Univ S Carolina, Hollings Canc Ctr, Canc Prevent & Control Program, Charleston, SC 29425 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2009年 / 18卷 / 12期

关键词：

OBSTRUCTIVE PULMONARY-DISEASE; PASSIVE SMOKING; TOBACCO-SMOKE; CHILDRENS EXPOSURE; INNATE-IMMUNITY; NEVER SMOKERS; DEFICIENCY; ASTHMA; POPULATION; WOMEN;

D O I：

10.1158/1055-9965.EPI-09-0986

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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)

引用

页码：3375 / 3383

页数：9

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