Association between periodontitis and breast cancer: two-sample Mendelian randomization study

Abstract

Objectives: The purpose of this study was to investigate whether there is a causal relationship between periodontitis and breast cancer by Mendelian randomization analysis. Materials and methods: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied complementary methods, including weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. Results: IVW MR analysis showed no effect of periodontitis on breast cancer (IVW OR=0.99, P =0.14). Similarly, no significant causal relationship between breast cancer and periodontitis was found in reverse MR analysis (IVW OR=0.95, P =0.83). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Based on sensitivity analyses, horizontal pleiotropy is unlikely to distort causal estimates. Conclusions: Although observational studies have reported an association between periodontitis and breast cancer, the results of our MR analysis do not support a causal relationship between periodontitis and breast cancer. Clinical relevance: Mendelian randomization study can more clearly analyze the causal relationship between periodontitis and breast cancer, in order to provide a certain reference for clinicians and deepen the understanding of the relationship between periodontitis and breast cancer, to explore more possible associations between periodontitis and systemic diseases.