Xiaodan Mai

Periodontal Disease and Breast Cancer: Prospective Cohort Study of Postmenopausal Women

Background: Periodontal disease 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 Womens 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. Periodontal disease was by self-report. HRs and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with periodontal disease 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. Periodontal disease, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14; 95% CI, 1.03–1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI, 1.05–1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI, 0.83–2.11); there were few cases (n = 74) and the CI included the null. The population attributable fraction was 12.06% (95% CI, 1.12–21.79) and 10.90% (95% CI, 10.31–28.94) for periodontal disease among former smokers quitting within 20 years and current smokers, respectively. Conclusion: Periodontal disease, 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. Cancer Epidemiol Biomarkers Prev; 25(1); 43–50. ©2015 AACR.

History of Periodontitis Diagnosis and Edentulism as Predictors of Cardiovascular Disease, Stroke, and Mortality in Postmenopausal Women

Background Few studies have reported associations between periodontitis and cardiovascular disease (CVD) risk in older women, which is the objective of the present investigation. Methods and Results Participants were 57 001 postmenopausal women ages 55 to 89 years (mean 68 years; >85% 60 and older) who were enrolled (1993–1998) in the Womens Health Initiative Observational Study, and were without known CVD when history of periodontitis and edentulism was assessed by questionnaire at study Year‐5 (1998–2003). There were 3589 incident CVD events and 3816 total deaths during a mean follow‐up of 6.7 years. In multivariable analysis, periodontitis was not associated with CVD events, but was associated with higher total mortality (hazard ratio (HR)=1.12, 95% CI: 1.05–1.21). Edentulism was associated with higher age‐ and smoking‐adjusted risks of CVD (HR=1.42, 95% CI: 1.27–1.59) and mortality (HR=1.47, 95% CI: 1.32–1.63). Further adjustment eliminated the association with CVD, but mortality remained significantly increased (HR=1.17, 95% CI: 1.02–1.33). Stratification on age, race‐ethnicity, smoking, and diabetes mellitus yielded comparable results; however, edentulism was more strongly associated with CVD in women reporting ≥1 dental visit (HR=1.57) compared with <1 visit (HR 1.03, interaction P=0.004) annually. Conclusions In community‐dwelling older women, edentulism was associated with increased risks of CVD and total mortality, and presence of periodontitis, which is more prevalent than edentulism, was associated with 17% higher mortality rate. These findings suggest that improving periodontal condition of the general population could reduce overall mortality.

Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Womens Health Initiative Observational Study. Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) 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: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255–65. ©2017 AACR.

Association of Serum 17β-Estradiol Concentration, Hormone Therapy, and Alveolar Crest Height in Postmenopausal Women

BACKGROUND Declines in endogenous estrogen levels after menopause can lead to systemic bone loss, including loss of oral bone and alveolar crest height (ACH). However, few studies have assessed both serum 17β-estradiol (E2) and exogenous hormone therapy (HT) use in relation to oral bone loss. METHODS This study examines the associations among serum E2, HT use, and ACH in 613 postmenopausal women from the Buffalo OsteoPerio study. Baseline ACH levels and 5-year ACH were assessed for groups according to E2 level (undetectable, >5.00 to ≤18.00, >18.00 to ≤46.07, and >46.07 pg/mL) and among HT use (never, ever) using analysis of variance and analysis of covariance. Logistic regression was used to analyze the association of ACH loss with serum E2 and HT use. RESULTS In cross-sectional analyses, no association was found of serum E2 with whole-mouth mean or worst-site ACH. However, history of HT use was associated with ACH. Women who had never used HT had more ACH loss assessed as a whole-mouth mean ACH (P = 0.01) and as worst-site ACH loss (P = 0.03). In logistic regression analyses of baseline ACH loss severity, HT never-users had two-fold higher odds of being in the severe ACH loss category compared to ever-users (odds ratio, 2.00; 95% confidence interval, 1.11 to 3.62). No association was observed of 5-year change in ACH with baseline serum E2 or HT use. CONCLUSION Although this study did not detect an association with current serum E2 level and ACH, HT use was found to be associated with less ACH loss in postmenopausal women.

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study.

BACKGROUND Extraoral translocation of oral bacteria may contribute to associations between periodontal disease and cancer. The associations among the presence of three orange-complex periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus), two red-complex periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia), and cancer risk were investigated. METHODS A total of 1,252 postmenopausal females enrolled in the Buffalo Osteoporosis and Periodontal Disease Study were followed prospectively. Baseline subgingival plaque samples were assessed for the presence of periodontal pathogens using indirect immunofluorescence. Incident cancer cases were adjudicated by staff physicians via review of medical records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of periodontal pathogens with total cancer and site-specific cancer risk in unadjusted and multivariable-adjusted models. RESULTS Neither the presence of individual pathogens nor the presence of any red-complex pathogens was associated with total cancer or site-specific cancers. Borderline associations were seen among the presence of any orange-complex pathogens (F. nucleatum, P. intermedia, and C. rectus), total cancer risk (HR = 1.35, 95% CI = 1.00 to 1.84), and lung cancer risk (HR = 3.02, 95% CI = 0.98 to 9.29). CONCLUSIONS No associations were found between the presence of individual subgingival pathogens and cancer risk. However, there were suggestions of borderline positive associations of the presence of any orange-complex pathogens with total cancer and lung cancer risk. The study is limited by the small number of cancer cases and the assessment of only five oral bacteria. Additional research is needed to understand the possible role of periodontal disease in carcinogenesis.

Vitamin D Status and Tooth Loss in Postmenopausal Females: The Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study

BACKGROUND Vitamin D is hypothesized to reduce risk for tooth loss via its influence on bone health, inflammation, and the immune response. The association between plasma 25-hydroxyvitamin D [25(OH)D] concentrations and prevalence and 5-year incidence of tooth loss in a cohort of postmenopausal females was examined. METHODS Participants underwent oral examinations at study baseline (1997 to 2000) and follow-up (2002 to 2005) to determine the number of missing teeth and 5-year incidence of tooth loss, respectively. At both visits, females self-reported reasons for each missing tooth. At baseline, 152 females reported no history of tooth loss, and 628 were categorized as reporting a history of tooth loss as a result of periodontal disease (n = 70) or caries (n = 558) (total n = 780). At follow-up, 96, 376, 48, and 328 females were categorized into the aforementioned categories related to tooth loss (total n = 472). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for tooth loss by category of baseline 25(OH)D (nmol/L) concentrations. Models were adjusted for age, income, smoking status, frequency of dental visits, waist circumference, and recreational physical activity. P value for trend was estimated using continuous concentrations of 25(OH)D. RESULTS Among females with 25(OH)D ≥50 (adequate vitamin D status) compared to <50 nmol/L (deficient/inadequate), the adjusted ORs were 1.24 (95% CI = 0.82 to 1.87), P-trend = <0.05 for the history (prevalence) of tooth loss resulting from periodontal disease or caries and 1.07 (95% CI = 0.62 to 1.85), P-trend = 0.11 for the incidence of tooth loss resulting from periodontal disease or caries. No statistically significant association was observed between 25(OH)D and the history or incidence of tooth loss caused by periodontal disease. An increased odds of the history of tooth loss attributable to caries was observed with increasing concentrations of 25(OH)D (P-trend = <0.05) but was not confirmed in prospective analyses. CONCLUSION In this cohort of postmenopausal females, the data do not support an association between vitamin D status and tooth loss.

Inaccurate self-report of height and its impact on misclassification of body mass index in postmenopausal women

Objective: Self-reported height is commonly used in population obesity research. Evidence has also shown a positive association between depression and obesity. We examined the extent of height misreporting and its impact on body mass index (BMI) calculations and classification, and explored whether depression is associated with height misreporting. Methods: The Buffalo Osteoporosis and Periodontal Disease Follow-up Study enrolled 1,015 postmenopausal women between 2002 and 2006. Participants self-reported their height on a questionnaire before stadiometer measurement at the clinical visit. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Odds ratios and 95% CI for association between depression and height misreporting were estimated using logistic regression. Results: Overall, 446 women (43.9%) misreported height by greater than 1/2 inch, of which 296 (29.2%) underestimated and 150 (14.8%) overestimated their height. Height misreporting influenced BMI calculations by ≥1 unit in 12% of women, and influenced classification into WHO BMI categories in 8% of women. After adjusting for age, race, education, and measured BMI, women with significant depressive symptoms were more likely to misreport their height (odds ratio = 1.65, 95% CI, 1.04-2.61). Conclusions: Height misreporting was common in older women and significantly influenced BMI calculations and classification. Obtaining objective data is thus important for studies investigating obesity-disease associations in this population, especially in those with significant depressive symptoms.

Abstract 848: Pathogenic oral bacteria and risk of incident cancer in postmenopausal women: The Buffalo OsteoPerio Study

Background: Periodontal disease (PD) has been found to be associated with increased cancer risk, including among participants in the Women9s Health Initiative (WHI). Microbial colonization of the subgingival area is a necessary causal factor for the development of PD. Previous findings of positive relationships between PD and cancer risk may be partially explained by extra-oral translocation of oral bacteria. We investigated the associations between the presence of three early-colonizing periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus, i.e., “orange complex” bacteria moderately associated with PD), two late-colonizing periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, i.e., “red complex” bacteria strongly associated with PD) and cancer risk in a subset of the WHI. Methods: We prospectively followed 1,252 postmenopausal women enrolled in the Buffalo OsteoPerio Study, an ancillary study of the WHI. Subgingival plaque samples were obtained during baseline oral examination from 1997 to 2000. Presence of periodontal pathogens was assessed using indirect immunofluorescence. Incident cancer cases through 2013 were identified via annual health updates and were confirmed using medical records by physician adjudicators. Cox proportional hazard regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of periodontal pathogens with total and site-specific cancer risk in crude and multivariate-adjusted models (adjusting for age and smoking status). Results: There were 171 confirmed incident cancer cases (invasive breast = 67, colorectal = 17, lung = 17) during an average follow-up of 11.8 years (SD = 3.8). When analyzed separately, individual pathogens were not associated with total or site-specific cancer. Presence of any pathogen was associated with increased lung cancer risk, although not statistically significant (adjusted HR = 3.97, 95% CI: 0.90-17.45). Presence of any late-colonizing pathogens was not statistically associated with total or site-specific cancer risks. After multivariate adjustment, there were borderline associations between presence of any early-colonizing pathogens and increased risk of total cancer (HR = 1.35, 95% CI: 1.00-1.84) and lung cancer (HR = 3.02, 95% CI: 0.98-9.29). Associations were not seen with invasive breast or colorectal cancer. Conclusions: We did not find consistent associations between presence of subgingival periodontal pathogens and risk of several cancers, but suggestion of associations with early colonizing pathogens for total and lung cancer. These conclusions are restricted by the small numbers of events and of bacteria evaluated. To clarify the present findings, further research is needed utilizing larger cohorts and more comprehensive assessment of presence and quantity of oral bacteria. Citation Format: Xiaodan Mai, Robert J. Genco, Michael J. LaMonte, Kathleen M. Hovey, Jo L. Freudenheim, Christopher A. Andrews, Jean Wactawski-Wende. Pathogenic oral bacteria and risk of incident cancer in postmenopausal women: The Buffalo OsteoPerio Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 848. doi:10.1158/1538-7445.AM2015-848

Abstract 256: Periodontal disease severity and incident cancer in postmenopausal women: the Buffalo OsteoPerio Study

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA 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 Womens 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