RESUMO
Background: Evidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis. Methods: The genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers. Results: We identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis. Conclusion: Our study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice.
RESUMO
WHAT IS KNOWN AND OBJECTIVE: Metformin has been suggested to confer anticancer efficacy. However, it remains uncertain whether additional use of metformin could improve survival of women with breast cancer. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the influence of metformin on survival outcome in women with breast cancer. METHODS: Relevant RCTs were obtained by search of PubMed, Embase and Cochrane's Library databases from inception to 15 May 2021. A random-effects model incorporating the potential publication bias was used to pool the results. RESULTS AND DISCUSSION: Five phase II RCTs including 396 non-diabetic women with breast cancer were included in the meta-analysis. Pooled results showed that additional use of metformin was not associated with improved progression-free survival (PFS, hazard ratio [HR]: 1.00, 95% confidence interval [CI]: 0.70 to 1.43, p = 0.98; I2 = 32%) or overall survival (OS, HR: 1.00, 95% CI: 0.71 to 1.39, p = 0.98; I2 = 0%). Sensitivity analysis by excluding one study at a time showed consistent results (HR for PFS: 0.91 to 1.14, p all >0.05; HR for OS: 0.88 to 1.21, P all >0.05). WHAT IS NEW AND CONCLUSION: Current evidence from phase II clinical trials does not support that additional use of metformin could improve the survival outcome in women with breast cancer.
