Introduction: Colorectal cancer (CRC) is a commonly diagnosed cancer, ranking third in prevalence among men and second among women. In the United States, CRC is the second leading cause of cancer-related deaths. Periodontal disease (PD), affecting a large number of adults, may increase cancer risk by the prolonged release of inflammatory mediators and increased carcinogen generation. Compared to normal colon tissue, an increased number of Fusobacterium nucleatum, a predominant subgingival microbial species in chronic periodontitis, was found in CRC tumors. Previous studies investigating the relationship between PD and CRC showed controversial conclusions. Thus, this meta-analysis was conducted.

Method: A comprehensive literature search on PubMed and Web of Science was conducted to identify all relevant studies published prior to November 2019 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate the association between the PD and CRC risk. Random effect or fixed effect model was used to calculate the pooled RR, based on heterogeneity significance. Subgroup analyses were conducted by study location, sample size, and outcome indicator. Meta-regression analysis was conducted to identify potential heterogeneity sources. Sensitivity analysis and publication bias detection were also performed. All analyses were performed with STATA, version 14.0 (Stata Corp, College Station, Tex) software, and all P values were two-tailed, the test level was 0.05.

Result: 674 articles were obtained from database searching and 4 articles were obtained from other sources. 15 articles with 17 studies involving 692,333 participants were included. 14 studies investigated incidence and 3 investigated mortality. All studies were considered moderate to high quality. All periodontal disease was determined by self-reported or clinical diagnosis. A significant association between PD and increased CRC incidence was found, with a pooled RR of 1.179 (95%CI: 1.036, 1.342, P=0.013, I2=84.7%). In subgroup analysis, the RR of 1 European study was 1.620 (95%CI, 1.128, 2.326, P=0.009), the pooled RR of 6 Asian studies was 1.258 (95%CI, 1.055, 1.500, P=0.011, I2=89.7%), and the pooled RR of 7 North American studies was 1.019 (95%CI: 0.931, 1.115, P=0.682, I2=0%). The pooled RR of 9 studies of sample size > 10,000 was 1.168 (95%CI: 1.004, 1.359, P=0.045, I2=88%), and the pooled RR of 5 studies of sample size ≤ 10,000 was 1.215 (95%CI: 0.896, 1.649, P=0.210, I2=77.3%). An insignificant association between PD and increased CRC mortality was found, with a pooled RR of 1.382 (95%CI: 0.734, 2.601, P=0.316, I2=53.5%). Meta-regression analysis indicated study locations and the number of confounding factor adjustment were potential heterogeneity sources. Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test, and Begg's test found no publication bias of analysis.

Conclusion: The current meta-analysis demonstrates a significant association between PD and increased incidence of CRC, indicating that early CRC screening is necessary for people with poor oral health, and oral health improvement might be beneficial for reducing CRC risk.

Citation Format: Chenyu Sun, Kun Xuan, Ankush R. Jha. Is periodontal disease associated with increased risk of colorectal cancer? A meta-analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1141.