mircoRNAs (miRNAs) play important roles on regulation of gene expressions. Aberrant expression of miRNAs was involved in various biological and pathological processes, including tumorigenesis of breast cancer. Single-nucleotide polymorphisms (SNPs) were implicated in altered expression or biological functions of mature miRNAs. To explore the relevance of miRNA polymorphisms and female physiological characteristics to breast cancer risk, SNPs located within hsa-miR-605 (rs2043556), hsa-miR-149 (rs2292832), hsa-miR-27a (rs895819), hsa-miR-196a-2 (rs11614913) and hsa-miR-618 (rs2682818) were selected, and their associations with breast cancer risk were analysed. In addition, associations between physiological characteristics-related factors and breast cancer risk were estimated too. We found that the ones with menarche age less than 16 years had increased breast cancer risk (OR = 2.10, 95% CI: 1.23-3.60). Marginally significant association between rs11614913 CT/CC genotypes and reduced breast cancer risk was observed (OR = 0.65, 95% CI: 0.40-1.06), while no significance was detected about the other miRNA polymorphisms. We concluded that menarche at less than 16 years old increased breast cancer risk, while the genetic variants in miR-196-a-2 might decrease the risk.

IntroductionThe oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis.MethodsSNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.ResultsNine gut microbiota taxa (Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales, Pasteurellales, Enterobacteriaceae, Pasteurellaceae, Bacteroidales S24.7 group, Alistipes, and Eisenbergiella) are predicted to play a causal role in enhancing the risk of periodontitis (p< 0.05). Besides, two gut microbiota taxa (Butyricicoccus and Ruminiclostridium 6) have potentially inhibitive causal effects on the risk of periodontitis (p< 0.05). No significant estimation of heterogeneity or pleiotropy is detected.ConclusionOur study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.