Periodontal and Other Oral Bacteria and Risk of Lung Cancer in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Evidence suggests that periodontal disease is associated with increased lung cancer risk, but whether periodontal pathogens are explanatory is unknown. We prospectively studied associations of pre-diagnostic circulating antibodies to oral bacteria and of periodontal bacteria in subgingival plaque with lung cancer. Methods: We included 4,263 cancer-free participants in the Atherosclerosis Risk in Communities study with previously measured serum IgG antibodies to 18 oral bacteria. In 1,287 participants for whom subgingival plaque was collected, counts for 8 periodontal bacteria were previously measured. Incident lung cancers (N=118) were ascertained through 2015 (median follow-up=17.5 years). We used Cox regression to estimate multivariable-adjusted associations, including for sums of antibodies to orange (C. rectus, F. nucleatum, P. intermedia, P. micra, P. nigrescens) and red (P. gingivalis, T. forsythensis, T. denticola) complex bacteria. Results: Orange complex bacteria antibodies were positively associated with lung cancer (per IQR HR=1.15, 95% CI 1.02-1.29), which was stronger in men (HR=1.27, 95% CI 1.08-1.49), and explained by P. intermedia and P. nigrescens (HR=1.15, 95% CI 1.04-1.26). Suggestive positive associations with lung cancer (N=40) were observed for F. nucleatum, A. actinomycetemcomitans, and P. gingivalis counts. Significant positive associations were found for count to antibody ratio for P. intermedia and P. gingivalis. Conclusions: We identified positive associations with lung cancer for oral bacteria, especially orange complex which are moderately pathogenic for periodontal disease. Impact: This prospective study supports the need for more research on periodontal bacteria in lung cancer etiology. If associations are supported, this may inform novel lung cancer prevention strategies.

Comparative analysis of antibodies to four major periodontal bacteria in respiratory diseases: a cohort study

“…A greater understanding is necessary as several studies have linked oral diseases to different systemic diseases 27 28. An association between lung cancer and periodontal and other oral bacteria has been studied in the Atherosclerosis Risk in Communities Study, which investigated IgG antibodies to 18 oral bacteria in 1287 participants 29. In a 17.5-year follow-up study, the authors found bacteria of the orange complex to be positively associated with lung cancer.…”

Circulating IgG antibodies to periodontal bacteria and lung cancer risk in the CLUE cohorts

“…naeslundii was inversely associated with overall cancer mortality. In a recent prospective cohort study on lung cancer risk ( 10 ), antibodies against P . intermedia and P .…”

“…gingivalis have been linked to increased risk of oropharyngeal cancers and mortality ( 8 , 9 ). In a recent cohort, a positive association was observed between antibodies to Prevotella intermedia and Porphyromonas nigrescens and risk of lung cancer (per interquartile range: hazard ratio = 1.15, 95% confidence interval [CI] = 1.04 to 1.26) ( 10 ).…”

Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases

“…In addition, statistical analysis showed a correlation between the presence of F. nucleatum and the risk of developing systemic cancers, especially lung cancer [ 82 ]. In a manner akin to the observations made regarding P. gingivalis , there exists a positive correlation between serum levels of IgG antibodies targeting F. nucleatum and the occurrence of lung cancer [ 71 ]. This alignment between the antibody levels and lung cancer underscores a potential association between F. nucleatum and the pathogenesis of lung cancer, meriting further investigation.…”

“…Furthermore, lung cancer patients with P. gingivalis infection also had significantly lower survival rates and median survival times [ 69 ]. Moreover, through the assessment of IgG antibodies specific to P. gingivalis within the serum of lung cancer patients, a positive correlation has been established between the levels of these antibodies and the susceptibility to developing lung cancer when contrasted with a cohort of healthy controls [ 70 , 71 ]. This intriguing link between the level of antibodies targeting P. gingivalis and the associated risk of lung cancer highlights a potential role of P. gingivalis in lung cancer pathogenesis.…”