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The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to evaluate the efficacy and safety of gabapentin versus placebo for pain control after total knee arthroplasty (TKA). In December 2015, a systematic computer-based search was conducted in the Medline, Embase, PubMed, Cochrane Controlled Trials Register (CENTRAL), Web of Science, Google, and Chinese Wanfang databases. This systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. The primary endpoint was the visual analogue scale (VAS) score after TKA with rest or mobilization at 24 and 48 hours, representing the efficacy of pain control after TKA. Cumulative morphine consumption via patient controlled anesthesia (PCA) was also assessed to determine the morphine-spare effect. Complications such as dizziness, pruritus, vomiting, nausea, and sedation were also compiled to assess the safety of gabapentin. Stata 12.0 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, the data were aggregated for random-effects modeling whenever necessary. Six studies involving 769 patients met the inclusion criteria. Our meta-analysis revealed that gabapentin resulted in superior pain relief compared to the control group in terms of VAS score with rest at 24 hours (mean difference [MD] = −3.47; 95% confidence interval [CI] −6.16 to −0.77; P = 0.012) and at 48 hours postoperatively (MD = −2.25; 95% CI −4.21 to −0.30; P = 0.024). There was no statistically significant difference between the groups with respect to the VAS score at 24 hours postoperatively (MD = 1.05; 95% CI −3.31 to 5.42; P = 0.636) or at 48 hours (MD = 1.71; 95% CI −0.74 to 4.15; P = 0.171). These results indicated that the perioperative administration of gabapentin decreases the cumulative morphine consumption via PCA at 24 hours (MD = −8.28; 95% CI −12.57 to −3.99; P = 0.000) and 48 hours (MD = −4.50; 95% CI −10.98 to −3.61; P = 0.221). Furthermore, gabapentin decreased the rate of postoperative dizziness (relative risk [RR], 0.68; 95% CI 0.47–0.99, P = 0.044) and the occurrence of pruritus (RR, 0.50; 95% CI 0.37–0.67, P = 0.000). Based on the current meta-analysis, gabapentin exerts an analgesic and opioid-sparing effect in acute postoperative pain management without increasing the rate of dizziness and pruritus.

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk. We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test. There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61–0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54–0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55–0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff–Bloom–Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively). Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.

MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52–0.86), recessive (OR = 0.65, 95% CI = 0.48–0.86), and allele models (OR = 0.73, 95% CI = 0.62–0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10–1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals.

Although interleukin (IL)-23 receptor (IL-23R) plays an important role in the pathogenesis of multiple cancers, its association with cancer risk is inconsistent across different studies. We therefore conducted a meta-analysis with the aim of resolving the relationship among the 3 common polymorphisms of IL-23R (rs6682925, rs10889677, rs1884444) and cancer risk. Case-control studies evaluating the association between IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) and cancer risk were searched in the PubMed, Web of Science, and CNKI databases. Data were included in the meta-analysis if they were from original studies adopting a case-control design investigating the association between IL-23R polymorphisms and risk of any cancer; all cancer cases must have been confirmed by histology or pathology, and controls selected from noncancer individuals. Case-only studies and review papers were excluded. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) with cancer risk. A random-effects model or fixed-effects model was used depending on the heterogeneity of the data. Ultimately, 15 studies, involving 8784 cancer patients and 10,321 cancer-free controls, were included in our meta-analysis. In the overall analysis, the rs10889677 polymorphism was associated with breast cancer (BC) under the allelic, homozygous, dominant, and heterozygous models. Rs1884444 polymorphism was relevant to hepatocellular carcinoma (HCC) under the homozygous, recessive, and allelic models. However, no evidence of a relationship between IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) and cancer risk was found in the overall population. Our meta-analysis provides no evidence supporting a global association of IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) with the risk of cancer. However, rs10889677 may be associated with BC susceptibility and rs1884444 had association with HCC risk. Further large and well-designed studies are warranted to confirm this finding.