Longbiao Zhu

Background: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I² statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73–0.81), the specificity was 0.81 (95% CI 0.73–0.86), the PLR was 3.99 (95% CI 2.81–5.65), the NLR was 0.28 (95% CI 0.23–0.35), the DOR was 14.18 (95% CI 8.47–23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81–0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68–0.86), the specificity was 0.85 (95% CI 0.78–0.90), and the AUC was 0.89 (95% CI 0.86–0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12–1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15–1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16–1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05–1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04–1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10–1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.

Objective: Long non‐coding RNA (lncRNA) MEG3 was associated with multiple types of cancers such as oral squamous cell carcinoma (OSCC). Single nucleotide polymorphisms (SNPs) might affect cancer risk by modifying the function of lncRNAs. But fewer study researched the relationship between SNPs and MEG3 in cancers. Considering these reasons, we supposed SNPs in MEG3 may influence the risk of OSCC.Material and Methods: The selected SNPs in MEG3 were genotyped in 1,428 subjects (444 patients with OSCC and 984 cancer‐free controls). The relationship between SNPs in MEG3 and OSCC risk was calculated by logistic regression analysis. The function of the SNPs was explored by luciferase activity assay.Results: A statistically significant increased risk was observed between rs11160608 and OSCC (Dominant model: adjusted OR = 1.36, 95% CI = 1.06–1.76, p = 0.017). Moreover, the effect of rs11160608 CC genotype with OSCC risk was much strong in drinkers than non‐drinkers (adjusted OR = 1.79, 95% CI = 1.17–2.73, p = 0.007). Furthermore, the luciferase activity of rs11160608 A allele was lower than rs11160608 C allele by luciferase reporter assay.Conclusion: Our study confirmed that the SNP rs11160608 in MEG3 might play an important role in OSCC by interring the binding of miRNA.

Breast cancer 1 (BRCA1) gene makes great contributions to the repair of DNA. The association between BRCA1 P871L polymorphism and cancer risk has been investigated in a growing number of studies, but the conclusions are not conclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 24 studies with 13762 cases and 22388 controls. The pooled results indicated that BRCA1 gene P871L variant decreased risk of overall cancer (homozygous model: odds ratio (OR) = 0.89, 95%confidence interval (CI) = 0.79-1.00; recessive model: OR = 0.89, 95% CI = 0.80-0.99). The stratified analysis observed decreased risk associated with BRCA1 P871L in subgroups among Asians and high score studies, but not Caucasians or low score studies. In conclusion, despite several limitations, this meta-analysis suggested that BRCA1 P871L genetic variation may be associated with decreased susceptibility to cancer.