儿童时期接触二手烟和功能性甘露糖结合凝集素多态性与肺癌风险增加有关。
Childhood exposure to secondhand smoke and functional mannose binding lectin polymorphisms are associated with increased lung cancer risk.
机构信息
Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD 20892-4258, USA.
出版信息
Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3375-83. doi: 10.1158/1055-9965.EPI-09-0986.
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.
背景
成年人接触二手烟会对健康造成有害影响，包括增加患肺癌的风险。与成年人相比，儿童可能更容易受到二手烟的影响。这种易感性可能会因先天免疫基因中遗传变异的改变而加剧，这些变异导致先天免疫系统中已知的功能变化。我们假设儿童时期接触二手烟与肺癌风险之间存在正相关关系，这种关系会受到甘露糖结合凝集素 2（MBL2）基因遗传多态性的修饰，从而导致先天免疫的已知功能变化。
方法
在正在进行的美国国立癌症研究所-马里兰州肺癌（NCI-MD）研究中，对男性和女性进行了儿童时期接触二手烟与肺癌风险的评估，该研究包括 624 例病例和 348 例对照。二手烟史通过面对面访谈收集。使用 DNA 对 MBL2 基因进行基因分型。为了复制，我们使用了梅奥诊所的一项独立的病例对照研究，该研究由从未吸烟的 461 人组成，其中包括 172 例病例和 289 例对照。所有统计检验均为双侧检验。
结果
在 NCI-MD 研究中，儿童时期接触二手烟与从不吸烟者的肺癌风险增加有关[比值比（OR），2.25；95%置信区间（95%CI），1.04-4.90]。这在梅奥研究中得到了证实（OR，1.47；95%CI，1.00-2.15）。一种与循环中 MBL 水平升高和 MBL2 活性增加相关的功能性 MBL2 单倍型与 NCI-MD 和 Mayo 研究中接触儿童时期二手烟的人群的肺癌风险增加相关（OR，2.52；95%CI，1.13-5.60，和 OR，2.78；95%CI，1.18-3.85）。
结论
儿童时期接触二手烟与从不吸烟者的肺癌风险增加有关，特别是在那些具有与先天免疫系统中已知过度活跃的补体途径相对应的单倍型的人群中。
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