Periodontitis and breast cancer risk: A systematic review with meta-epidemiological analysis.
BACKGROUND The association between periodontitis and breast cancer (BC) risk has been reported, but with considerable variability in effect estimates across studies. This meta-epidemiological study aimed to systematically evaluate how methodological characteristics of primary studies influence these reported effect estimates. METHODS Cohort and case-control studies were searched in electronic databases up to February 2025. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses were conducted to estimate risk measures (relative risk [RR] and 95% confidence intervals [CI]). Meta-regression and subgroup analyses were performed to investigate potential variability in effect estimates. RESULTS Among the 19 included studies, although the overall pooled estimate indicated a 19% higher risk of BC in women with periodontitis compared with those without periodontitis (RR = 1.19; 95%CI, 1.05-1.34), meta-epidemiological analyses showed attenuated estimates in prospective vs. case-control studies (RR = 1.05 vs. 1.54), high- vs. moderate-quality studies (RR = 1.09 vs. 2.10), and adjusted vs. unadjusted analyses (RR = 1.07 vs. 1.48) (p < 0.05). CONCLUSION Although a small association between periodontitis and BC risk was observed, its magnitude appears to be overestimated in lower-quality, case-control, and inadequately adjusted studies. These findings underscore the importance of methodological rigor in the interpretation of the evidence. PLAIN LANGUAGE SUMMARY This meta-epidemiological study, based on a systematic and rigorous literature search, confirmed a modest association between periodontitis and increased breast cancer risk. The strength of this association appears to be inflated by methodological limitations in the primary studies, particularly in case-control designs and in studies with limited adjustment for confounding factors. These findings emphasize the need for high-quality prospective studies to more accurately characterize this relationship.