Hjalgrim Henrik, Ekström-Smedby Karin, Rostgaard Klaus, Amini Rose-Marie, Molin Daniel, Hamilton-Dutoit Stephen, Schöllkopf Claudia, Chang Ellen T, Ralfkiaer Elisabeth, Adami Hans-Olov, Glimelius Bengt, Melbye Mads
Department of Epidemiology Research, Statens Serum Institut, University of Copenhagen, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1561-6. doi: 10.1158/1055-9965.EPI-07-0094.
Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship.
We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders.
Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; P(homogeneity EBV-pos) versus P(homogeneity EBV-neg) = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group.
The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.
关于吸烟与霍奇金淋巴瘤（HL）风险之间的关联，各项研究报告结果并不一致。相互矛盾的研究结果可能反映了HL各亚型之间病因的异质性，因此有必要进一步明确二者之间的关系。
在一项丹麦-瑞典病例对照研究中，我们收集了586例经典型HL患者和3187名对照人群的吸烟习惯信息。采用标准技术确定了499例患者的HL-EBV状态。通过逻辑回归分析计算吸烟与HL总体关联的比值比（OR），并按年龄、性别、主要组织学亚型和肿瘤EBV状态进行分层，同时对已知的混杂因素进行校正。
与从不吸烟者相比，当前吸烟者患HL的总体风险增加[校正OR，1.57；95%置信区间（95%CI），1.22-2.03]。这种关联在EBV阳性HL中最为显著（校正OR，2.36；95%CI，1.51-3.71），但在EBV阴性HL中也存在（校正OR，1.43；95%CI，1.05-1.97；P（EBV阳性的同质性）与P（EBV阴性的同质性）=0.04）。该关联在年龄、性别或组织学亚型方面没有明显差异，在所有分层中均存在明显的EBV相关差异。无论从开始吸烟的年龄、每日吸烟量、吸烟年限还是累积吸烟量来看，均未发现剂量反应模式的证据。在以参与基础研究的非HL患者（n=3055）作为对照组的分析中，也得到了类似的结果。
观察到的吸烟与HL风险之间的关联与先前的研究结果一致，且在生物学上具有可信度。尽管不太可能被视为人为因素，但剂量反应模式的证据有限，使得因果关系的总体证据较弱。
