Two-Sample Mendelian Randomization Analysis of Associations Between Periodontal Disease and Risk of Cancer

Background: Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a two-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks.

Methods: Our primary instrument included single nucleotide polymorphisms (SNPs) with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n=58,131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium; Colon Cancer Family Registry; and Colorectal Transdisciplinary study), lung cancer (n=18,082 cases; International Lung Cancer Consortium), and pancreatic cancer (n=9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse‐variance weighted (primary analyses), MR-PRESSO, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer sub-type (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided.

Results: The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; p=0.03), 3% increased risk of colon cancer (p=0.02), 4% increased risk of proximal colon cancer (p=0.01), and 3% increased risk of colorectal cancer among females (p=0.04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups.
Conclusions: Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted.