Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD 20852, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1498-505. doi: 10.1158/1055-9965.EPI-09-1261. Epub 2010 May 25.
We evaluated the relationship of Chlamydia pneumoniae infection with prospective lung cancer risk using traditional serologic markers [microimmunoflourescence (MIF) IgG and IgA antibodies] and Chlamydia heat shock protein-60 (CHSP-60) antibodies, a marker for chronic chlamydial infection.
We conducted a nested case-control study (593 lung cancers and 671 controls) within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to cases by age, sex, randomization year, follow-up time, and smoking (pack-years of smoking, time since quitting). We assessed C. pneumoniae seropositivity and endpoint antibody titers (IgG and IgA against C. pneumoniae elementary bodies and IgG against CHSP-60).
C. pneumoniae seropositivity by microimmunoflourescence IgG or IgA antibodies was not associated with lung cancer [odds ratio of 0.88 and 95% confidence interval (95% CI) of 0.69-1.13 for IgG; odds ratio of 0.98 and 95% CI of 0.75-1.27 for IgA]. In contrast, individuals seropositive for CHSP-60 IgG antibodies had significantly increased lung cancer risk (odds ratio, 1.30; 95% CI, 1.02-1.67), and risk increased with increasing antibody titers (P trend = 0.006). CHSP-60-related risk did not differ significantly by lung cancer histology, follow-up time, or smoking. CHSP-60 seropositivity was associated with increased risk 2 to 5 years before lung cancer diagnosis (odds ratio, 1.77; 95% CI, 1.16-2.71; P trend = 0.006), thus arguing against reverse causality.
CHSP-60 seropositivity and elevated antibody titers were associated with significantly increased risk for subsequent lung cancer, supporting an etiologic role for C. pneumoniae infection in lung carcinogenesis.
Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation.
我们使用传统的血清学标志物（微量免疫荧光法 IgG 和 IgA 抗体）和沙眼衣原体热休克蛋白 60（CHSP-60）抗体（慢性衣原体感染的标志物）评估肺炎衣原体感染与肺癌风险的关系。
我们在前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验（N=77464）的筛查组中进行了一项巢式病例对照研究（593 例肺癌和 671 例对照）。对照组与病例按年龄、性别、随机化年份、随访时间和吸烟情况（吸烟包年数、戒烟时间）匹配。我们评估了肺炎衣原体血清阳性和终点抗体滴度（针对肺炎衣原体原体的 IgG 和 IgA 抗体以及针对 CHSP-60 的 IgG 抗体）。
肺炎衣原体微量免疫荧光 IgG 或 IgA 抗体阳性与肺癌无关[IgG 的比值比（OR）为 0.88，95%置信区间（95%CI）为 0.69-1.13；IgA 的 OR 为 0.98，95%CI 为 0.75-1.27]。相比之下，CHSP-60 IgG 抗体阳性的个体肺癌风险显著增加（OR，1.30；95%CI，1.02-1.67），且抗体滴度升高风险也增加（P 趋势=0.006）。CHSP-60 相关风险与肺癌组织学、随访时间或吸烟情况无显著差异。CHSP-60 阳性与肺癌诊断前 2-5 年风险增加相关（OR，1.77；95%CI，1.16-2.71；P 趋势=0.006），因此排除了反向因果关系。
CHSP-60 血清阳性和抗体滴度升高与随后肺癌风险显著增加相关，支持肺炎衣原体感染在肺癌发生中的病因作用。
我们的研究结果突出了通过针对肺炎衣原体感染和慢性肺部炎症的治疗来降低肺癌风险的潜力。
