Background: 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. Methods: 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). Results: 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 seropositivitywas 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. Conclusions: 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. Impact: Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation.
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