Abstract Background: Periodontal disease has an infectious etiology and there is growing evidence that it may be positively associated with cancer occurrence. Potential mechanisms may involve the host inflammatory response to oral infection and the potential mobility of the oral microbiome to extra-oral sites. However, few studies have focused on older postmenopausal women who are susceptible to both periodontal disease and cancer and where comprehensive periodontal assessments have been made. This study aims to determine whether loss of alveolar crestal bone height (ACH) in the oral cavity, a measure of chronic periodontitis, is associated with incident cancer in a well-characterized cohort of postmenopausal women. Methods: We prospectively followed a cohort of 1,337 postmenopausal women (aged 53-85 years at baseline; 3% current smokers) who participated in the Buffalo OsteoPerio Study, an ancillary study of the Women's Health Initiative. Whole mouth mean and worst site ACH (mm of loss) were assessed from oral radiographs. Incident cancer was ascertained from annual health updates and confirmed using medical records by physician adjudicators. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of ACH with total and site-specific cancer risk in multivariate-adjusted models. Results: During an average follow-up of 9.6 years (SD=2.7), there were 170 confirmed incident cancer cases. The most common sites were breast (N=77), lung (N=15), colorectum (N=14), and endometrium (N=12), accounting for 69% of all cancers. When analyzed as a continuous exposure and after adjusting for age, education, and pack-years of smoking, worst site ACH was not associated with total cancer risk (HR=1.04 per 1mm loss, 95% CI=0.94-1.15). However, there was a statistically significant increased risk of lung (HR=1.49, 95% CI=1.18-1.89) and colorectal cancer (HR=1.35, 95% CI=1.04-1.74). No associations were found for worst site ACH with breast (HR=0.91, 95% CI=0.77-1.09) or endometrial cancer (HR=0.77, 95% CI=0.46-1.30). Whole mouth mean ACH was also significantly associated with incident lung cancer (HR=2.05 per 1mm loss, 95% CI=1.40-3.01), but not with total cancer (HR=1.09, 95% CI=0.89-1.33), or with colorectal (HR=1.45, 95% CI=0.91-2.33), breast (HR=0.83, 95% CI=0.57-1.20) or endometrial (HR=0.62, 95% CI=0.21-1.85) cancers in multivariate-adjusted models. These estimates did not change appreciably after further adjustments. Conclusions: This study provides evidence that chronic periodontitis is positively associated with risk of lung and colorectal cancer in postmenopausal women. These results need to be interpreted cautiously given the small number of incident cancer cases. Further research utilizing a larger sample is warranted to confirm these results. Citation Format: Xiaodan Mai, Jo L. Freudenheim, Michael J. LaMonte, Kathleen M. Hovey, Christopher A. Andrews, Robert J. Genco, Jean Wactawski-Wende. Periodontal disease severity and incident cancer in postmenopausal women: the Buffalo OsteoPerio Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 256. doi:10.1158/1538-7445.AM2014-256