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

Laura Corlin, Mengyuan Ruan, Kostas Tsilidis, Emmanouil Bouras, Yau-Hua Yu, Rachel Stolzenberg-Solomo, Alison P. Klein, Harvey A. Risch, Christopher I. Amos, Lori C Sakoda, Pavel Vodicka, Pai K. Rish, James Beck, Elizabeth A. Platz, Dominique S Michaud*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Article numberpkab037
Number of pages8
JournalJournal of the National Cancer Institute
Issue number3
Publication statusPublished - 19 Apr 2021

Structured keywords

  • ICEP


  • smoking
  • lung
  • cancer
  • colorectal cancer
  • Genetic Predisposition to Disease
  • periodontal disease
  • periodontitis
  • single nucleotide polymorphism
  • genetics
  • lung cancer
  • colon cancer
  • pancreatic cancer
  • pleiotropism
  • Cancer risk
  • Genome wide association study
  • Mendelian randomisation analysis


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