Background Periodontal pathogens have been isolated from pre-cancerous and cancerous lesions and also shown to promote a pro-carcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer and none has focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women’s Health Initiative Observational Study. Methods Our prospective cohort study comprised 65,869 women, aged 54–86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, while ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancer were the main outcomes and site-specific cancers were secondary outcomes. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. All analyses were conducted two-sided. Results During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk [multivariable adjusted HR 1.14, 95% CI 1.08–1.20]; findings were similar in analyses limited to 34,097 never smokers [HR 1.12, 95% CI 1.04–1.22]. Associations were observed for breast [HR 1.13, 95% CI 1.03–1.23]; lung [HR 1.31, 95% CI 1.14–1.51]; esophagus [HR 3.28, 95% CI 1.64–6.53]; gallbladder [HR 1.73, 95% CI 1.01–2.95]; and melanoma skin [HR 1.23, 95% CI 1.02–1.48] cancers; Stomach cancer was borderline [HR 1.58, 95% CI 0.94–2.67]. Conclusions and Impact Periodontal disease increases risk of total cancer among older women, irrespective of smoking. Certain anatomic sites appear to be vulnerable and warrant further investigation.

Purpose Few prospective studies have reported on relationships between objective periodontal disease (PD) measures and cancer risk. This association was examined in 1,337 postmenopausal women participating in the Buffalo OsteoPerio Study. Methods Oral alveolar crestal bone height (ACH) was measured using oral radiographs. Incident cancers were adjudicated with medical records. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between ACH and incident cancer outcomes were estimated using Cox proportional hazards models. Results There were 203 confirmed total incident cancer cases during follow-up (12.2±4.2 years). After adjusting for age and smoking, there were no statistically significant associations between ACH-defined PD categories and total cancer risk (mild/moderate vs. none: HR=1.33, 95%CI: 0.91–1.94; severe vs. none: HR=1.20, 95%CI: 0.77–1.86). ACH-defined PD categories were not associated with common site-specific cancers. Whole mouth mean and worst site ACH (per 1mm loss) were significantly associated with increased risk of lung (adjusted HR=1.81, 95% CI: 1.30–2.54; adjusted HR=1.34, 95% CI: 1.08–1.66, respectively), but not total or other site-specific cancer. Smoking status modified the associations between continuous ACH variables and total cancer risk; measures of PD were associated with total cancer among smokers but not never-smokers (interaction p=0.02 and p<0.01 for whole mouth mean and worst site ACH, respectively). Conclusions ACH-defined PD was associated with total cancer risk in ever but not never-smoking postmenopausal women. Whole mouth mean and worst site ACH were associated with increased lung cancer risk. However, these results need to be interpreted cautiously given the small number of lung cancer cases (n=18). Further research utilizing a larger sample is warranted to confirm the relationships among oral bone loss, site-specific cancers, and total cancer.

Background Periodontal disease (PD) has been consistently associated with chronic disease; there are no large studies of breast cancer although oral-associated microbes are present in breast tumors. Methods In the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, 73,737 women without previous breast cancer were followed. Incident, primary, invasive breast tumors were verified by physician adjudication. PD was by self-report. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with PD differs with smoking status, we examined associations stratified by smoking. Results 2,124 incident, invasive breast cancer cases were identified after mean follow-up of 6.7 years. PD, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14, 95% CI 1.03 to 1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI 1.05 to 1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI 0.83 to 2.11); there were few cases (n=74) and the CI included the null. The population attributable fraction was 12.06% (95% CI 1.12 to 21.79) and 10.90% (95% CI 10.31 to 28.94) for PD among former smokers quitting within 20 years and current smokers, respectively. Conclusion PD, a common chronic inflammatory disorder, was associated with increased risk of postmenopausal breast cancer, particularly among former smokers who quit in the past 20 years. Impact Understanding a possible role of the oral microbiome in breast carcinogenesis could impact prevention.

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Purpose While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women. Methods Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. History of PD (prevalence of 26.1%) was self-reported and 754 incident lung cancer cases occurred during an average 6.8 (SD ±2.6) years of follow-up. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR=1.24, 95% CI: 1.07–1.45). There was a positive additive interaction between PD with pack-years of smoking (P=0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR=1.02, 95% CI: 0.68–1.53). Conclusions PD was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.