Low level of antibodies to the oral bacterium Tannerella forsythia predicts bladder cancers and Treponema denticola predicts colon and bladder cancers: A prospective cohort study

Abstract

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.

Fig 1. Number of incident cancer cases of bladder by quartile antibody levels of Tannerella forsythia (TF).

Quartile (Q) values are Q1 9–35, Q2 36–58, Q3 59–104, Q4 105–1204.

Fig 2. Number of incident cancer cases of bladder and colon by quartile antibody levels of Treponema denticola (TD).

Quartile (Q) values are Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240.

Fig 3. Frequency of incident cancer cases (n = 113) per quartile antibody levels of the oral bacteria Tannerella forsythia (TF), Porphyromonas gingivalis (PG), Treponema denticola (TD) and Aggregatibacter actinomycetemcomitans (AA).

Quartile (Q) levels: TF Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240, TD Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240, PG Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240., AA Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240.

Fig 4. Frequency of non-cancer participants (n = 508) per quartile antibody levels of the oral bacteria Tannerella forsythia (TF), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Aggregatibacter actinomycetemcomitans (AA).

Quartile (Q) levels: TF Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240, TD Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240, PG Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240., AA Q1 1–28, Q2 29–44, Q3 45–73, Q4 74–1240.

Fig 5. Overall cumulative cancer incidence stratified on quartiles of Tannerella forsythia antibody levels.

Fig 6. Overall cumulative cancer incidence stratified on quartiles of Treponema denticola antibody levels.