The effect of CYP3A4 genetic variants on the susceptibility to chronic obstructive pulmonary disease in the Hainan Han population

PurposeGenetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk.MethodsWe carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI).ResultsOur study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10–1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19–3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31–0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12–2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45–0.90, p = 0.010). Haplotype analysis revealed that A_rs4646440T_rs35564277 haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04–2.82, p = 0.034).ConclusionOur result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.     

Cardiovascular toxicity following immune checkpoint inhibitors: A systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors may be associated with multiple immune-related toxicities. Cardiovascular adverse effects are underreported in clinical trials.MethodsWe conducted a systematic review and meta-analysis to evaluate cardiovascular adverse effects incidence among patients with solid tumors receiving immune checkpoint inhibitors in randomized clinical trials and the relative risk of presenting these effects compared to placebo or best supportive care. The search was conducted through MEDLINE, Embase, and Scopus databases from January 1st, 2010 until July 1st, 2020. Outcomes were reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Results57 randomized clinical trials including 12,118 patients were included. All grade CV AEs incidence rate was 8.32% (95% CI = 6.35%-10.53%). When only grade 3–5 CV AEs were considered, ICIs were significantly associated with increased risk than placebo or BSC (RR = 1.36; 95% CI = 1.06–1.73; p = 0.01).ConclusionThis meta-analysis corroborates the hypothesis of increased CV risk related to immune checkpoint inhibitors.     

Effect of Low-Frequency rTMS on Aphasia in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials

Background

Small clinical trials have reported that low-frequency repetitive transcranial magnetic stimulation (rTMS) might improve language recovery in patients with aphasia after stroke. However, no systematic reviews or meta-analyses studies have investigated the effect of rTMS on aphasia. The objective of this study was to perform a meta-analysis of studies that explored the effects of low-frequency rTMS on aphasia in stroke patients.

Methods

We searched PubMed, CENTRAL, Embase, CINAHL, ScienceDirect, and Journals@Ovid for randomized controlled trials published between January 1965 and October 2013 using the keywords “aphasia OR language disorders OR anomia OR linguistic disorders AND repetitive transcranial magnetic stimulation OR rTMS”. We used fixed- and random-effects models to estimate the standardized mean difference (SMD) and a 95% CI for the language outcomes.

Results

Seven eligible studies involving 160 stroke patients were identified in this meta-analysis. A significant effect size of 1.26 was found for the language outcome severity of impairment (95% CI = 0.80 to 1.71) without heterogeneity (I² = 0%, P = 0.44). Further analyses demonstrated prominent effects for the naming subtest (SMD = 0.52, 95% CI = 0.18 to 0.87), repetition (SMD = 0.54, 95% CI = 0.16 to 0.92), writing (SMD = 0.70, 95% CI = 0.19 to 1.22), and comprehension (the Token test: SMD = 0.58, 95% CI = 0.07 to 1.09) without heterogeneity (I² = 0%). The SMD of AAT and BDAE comprehension subtests was 0.32 (95% CI = −0.08 to 0.72) with moderate heterogeneity (I² = 32%,P = 0.22). The effect size did not change significantly even when any one trial was eliminated. None of the patients from the 7 included articles reported adverse effects from rTMS.

Conclusions

Low-frequency rTMS with a 90% resting motor threshold that targets the triangular part of the right inferior frontal gyrus (IFG) has a positive effect on language recovery in patients with aphasia following stroke. Further well-designed studies with larger populations are required to ascertain the long-term effects of rTMS in aphasia treatment.     

Vitamin D receptor ApaI,TaqI, BsmI,and FokI polymorphisms and psoriasis susceptibility: a meta-analysis

The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted on the associations between the VDR ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis. Nine relevant studies on VDR polymorphisms and psoriasis were included in this meta-analysis, which involved 742 psoriasis patients and 715 controls. Meta-analysis indicated an association between the VDR ApaI A allele and psoriasis in Turkish studies (OR = 0.684, 95% CI = 0.475–0.985, p = 0.041). Meta-analysis indicated an association between the BsmI B allele and psoriasis in Asians (OR = 0.636, 95% CI = 0.411–0.984, p = 0.041), and showed a significant association between the FF and ff genotypes of the FokI polymorphism and psoriasis in all study subjects and in Turkish studies (OR = 2.028, 95% CI = 1.194–3.446, p = 0.009; OR = 3.582, 95% CI = 1.602–8.009, p = 0.002). This meta-analysis suggests that the VDR ApaI polymorphism confers susceptibility to psoriasis in the Turkish population. In addition, associations were found between the BsmI polymorphism and susceptibility to psoriasis in Asians and between the Fok I polymorphism and psoriasis in the Turkish population.     

A Meta-Analysis of P2X7 Gene-762T/C Polymorphism and Pulmonary Tuberculosis Susceptibility

AimWe performed a comprehensive meta-analysis to determine the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis susceptibility.MethodologyBased on comprehensive searches of the PubMed, SCI, Elsevier, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis risk. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated in random-effects model.ResultsA total of 2207 tuberculosis cases and 2220 controls in 8 case-control studies were included in this meta-analysis. Allele model (C vs. T: p = 0.15; OR = 0.83, 95% CI = 0.65–1.07), homozygous model (CC vs. TT: p = 0.23; OR = 0.73, 95% CI = 0.44 to 1.22), and heterozygous model (CT vs. TT: p = 0.57; OR = 0.92, 95% CI = 0.68 to 1.24) did not show increased risk of developing pulmonary tuberculosis. Similarly, dominant model (CC+CT vs. TT: p = 0.32; OR = 0.84, 95% CI = 0.59 to 1.19) and recessive model (CC vs. CT+TT: p = 0.08; OR = 0.77, 95% CI = 0.57 to 1.04) failed to show increased risk of developing pulmonary tuberculosis. Subgroup analysis by ethnicity did not detect any significant association between P2X7–762T/C polymorphism and pulmonary tuberculosis susceptibility.ConclusionsP2X7 -762T/C gene polymorphism is not associated with pulmonary tuberculosis susceptibility.     

Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case–control studies

Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk.     

Evaluation of Zhilong Huoxue Tongyu capsule in the treatment of acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials

BackgroundZhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine and used for the treatment of acute cerebral infarction (ACI) and its clinical application has gradually been widely recognized in China. However, the effects of ZL for patients with ACI have never been systematically evaluated.PurposeA systematic review and meta-analysis was performed to evaluate the efficacy of ZL in ACI.Study designA systematic review and meta-analysis of randomized clinical trials (RCTs).Materials and methodsA systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The comprehensive literature search was accomplished in 6 electronic databases to find relevant randomized controlled trials from their inception until October 31, 2020. The Cochrane Handbook for Systematic Reviews of Interventions was used for methodological quality and independent evaluation. Review Manager 5.3 was used to analyze all the data obtained. The Clinical Effective Rate (CER) was the primary outcome, and the National Institutes of Health Stroke Score (NIHSS), Barthel Index (BI), and Modified Rankin Scale (MRS) were the secondary outcomes.ResultsSeven clinical studies recruiting 571 eligible patients were included in this meta-analysis. The results of meta-analysis suggested that compared with conventional treatment alone, ZL combined with conventional treatment significantly improved CER (RR = 1.20, 95% CI: 1.12-1.29, p < 0.00001), decrease National Institutes of Health Stroke Scale Score (NIHSS) (MD = -2.60, 95% CI: -3.41–1.79, p < 0.00001), Barthel Index (BI) (MD = -9.75, 95% CI: 7.15-12.36, p < 0.00001) and Modified Rankin Scale (MRS) (MD = -0.57, 95% CI: -0.84–0.30, p < 0.00001). There were no reported adverse events in the studies. Most results were robust and the quality of evidence was from moderate to low.ConclusionZL combined with conventional treatment can improve the short-term outcomes of ACI patients, indicating ZL is a promising treatment choice for ACI and may be used as adjunctive treatment to the conventional treatment of ACI. However, due to the limitations of included clinical trials, high-quality clinical trials with longer follow-ups are still needed to further assess the effectiveness and safety of ZL for ACI patients.     

Influence of interleukin-6 gene − 174G>C polymorphism on development of atherosclerosis: A meta-analysis of 50 studies involving 33,514 subjects

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene − 174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene − 174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene − 174G>C polymorphism and AS risk (for C allele vs. G allele: OR = 1.02, 95% CI = 0.94–1.11, p = 0.64; for C/C vs. G/G: OR = 1.01, 95% CI = 0.85–1.21, p = 0.88; for C/C vs. C/G + G/G: OR = 0.97, 95% CI = 0.84–1.12, p = 0.68; for C/C + C/G vs. G/G: OR = 1.07, 95% CI = 0.97–1.17, p = 0.18). In the subgroup analyses, significant associations were found between the IL-6 gene − 174G>C polymorphism and AS in non-Caucasian group (for CC + CG vs. GG: OR = 1.22, 95% CI = 1.06–1.41, p = 0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR = 0.75, 95% CI = 0.61–0.93, p = 0.008; for C/C vs. G/G: OR = 0.56, 95% CI = 0.38–0.81, p = 0.002; for C/C vs. C/G + G/G: OR = 0.60, 95% CI = 0.45–0.79, p = 0.0004) and population-based group (for C allele vs. G allele: OR = 1.09, 95% CI = 1.00–1.18, p = 0.04; for CC + CG vs. GG: OR = 1.15, 95% CI = 1.04–1.27, p = 0.005). In summary, the present meta-analysis suggests that the IL-6 gene − 174G C polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.     

Lack of association between glutathione S-transferase T1 gene polymorphism and laryngeal cancer susceptibility: a meta-analysis based on 2,124 cases and 2,059 controls

Studies investigating the association between glutathione S-transferase T1 (GSTT1) gene polymorphism and laryngeal cancer susceptibility have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of GSTT1 gene polymorphism with laryngeal cancer risk. The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011. Twelve studies were included in the present meta-analysis, which described a total of 2124 laryngeal cancer cases and 2059 controls. The overall odds ratio (OR) for GSTT1 null genotype was 1.40 (95% CI = 0.90-2.16). When stratifying for race, the pooled ORs for GSTT1 null genotype were 1.07 (95% CI = 0.81-1.41) in Caucasians and 5.63 (95% CI = 1.00-31.83) in Asians. The pooled ORs for GSTT1 null genotype were 1.03 (95% CI = 0.71-1.49) in population-based studies and 2.39 (95% CI = 0.73-7.86) in hospital-based studies, stratifying for study design. This meta-analysis suggested that there was lack of association between GSTT1 gene polymorphism and laryngeal cancer risk. However, larger scale primary studies are still required to further evaluate the interaction of GSTT1 gene polymorphism with laryngeal cancer risk.     

Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case–control studies

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04–1.16) and in additive model (OR = 1.10, 95% CI = 1.03–1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82–0.99) and dominant model (OR = 0.94, 95% CI = 0.89–0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.     

<Emphasis Type="Italic">TGFBR1</Emphasis>*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls

Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03–1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01–1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01–1.15; for dominant model: OR = 1.08; 95% CI = 1.02–1.15; for recessive model: OR = 1.29; 95% CI = 1.00–1.68). In the subgroup analysis by cancer types, significant associations were found in breast cancer (for allelic effect: OR = 1.16; 95% CI = 1.01–1.34) and ovarian cancer (for allelic effect: OR = 1.24; 95% CI = 1.00–1.54; for 6A/6A vs. 9A/9A: OR = 2.34; 95% CI = 1.03–5.33). However, no significant associations were found in colorectal cancer, bladder cancer, prostate cancer and lung cancer for all genetic models. In summary, this meta-analysis suggests that the TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer.     

Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis

Background

Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG.

Methods

Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model.

Results

14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR = 1.19, 95% CI = 0.82–1.73, p = 0.361; GSTT1: OR = 1.26, 95% CI = 0.77–2.06, p = 0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR = 1.41, 95% CI = 1.04–1.90, p = 0.026), but not in Caucasians (OR = 1.13, 95% CI = 0.69–1.84, p = 0.638) and Latin-American (OR = 1.09, 95% CI = 0.62–1.92, p = 0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population.

Conclusions

The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians.     

Alterations in peripheral joint muscle force control in adults with musculoskeletal disease,injury, surgery,or arthroplasty: A systematic review and meta-analysis

PurposeTo systematically review and analyse whether musculoskeletal conditions affect peripheral joint muscle force control (i.e. magnitude and/or complexity of force fluctuations).MethodsA literature search was conducted using MEDLINE, CINAHL and SPORTDiscus databases (from inception-8th April 2021) for studies involving: 1) participants with musculoskeletal disease, injury, surgery, or arthroplasty in the peripheral joints of the upper/lower limb; 2) comparison with an unaffected control group or unaffected contralateral limb; and 3) measures of the magnitude and/or complexity of force fluctuations during targeted isometric contractions. The methodological quality of studies was evaluated using a modified Downs and Black Quality Index. Studies were combined using the standardized mean difference (SMD) in a random-effects model.Results14 studies (investigating 694 participants) were included in the meta-analysis. There was a significant effect of musculoskeletal conditions on peripheral joint muscle force coefficient of variation (CV; SMD = 0.19 [95 % CI 0.06, 0.32]), whereby individuals with musculoskeletal conditions exhibited greater CV than controls. Subgroup analyses revealed that CV was only greater: 1) when comparison was made between symptomatic and asymptomatic individuals (rather than between affected and contralateral limbs; SMD = 0.22 [95 % CI 0.07, 0.38]); 2) for conditions of the knee (SMD = 0.29 [95 % CI 0.14, 0.44]); and 3) for ACL injury post-surgery (SMD = 0.56 [95 % CI 0.36, 0.75]).ConclusionMusculoskeletal conditions result in an increase in peripheral joint muscle force CV, with this effect dependent on study design, peripheral joint, and surgical status. The greater force CV is indicative of decreased force steadiness and could have implications for long-term tissue health/day-to-day function.     

Running-related muscle activation patterns and tibial acceleration across puberty

This study examined whether differences exist in tibial acceleration transients and electromyography (EMG) variables during running across female pubertal development. Sixty-four girls classified as pre- (n = 19), early/mid- (n = 22) and late/post-pubertal development (n = 23) ran in a laboratory whilst EMG data were recorded from quadriceps, hamstring and calf muscle groups, and acceleration transients from a triaxial accelerometer. The late/post-pubertal girls exhibited delayed vastus lateralis onset (mean difference (MD) = 0.02, 95% CI = 0.008, 0.34 ms)) compared to pre-pubertal girls, lower vastus lateralis pre-activation (MD = 7.02, 95% CI = 12.63, 1.42%) compared to early/mid-pubertal girls, and longer time to peak (TTP) anterior/posterior (A/P) tibial acceleration compared to pre-pubertal girls (MD = 0.02, 95% CI = 0.006, 0.03 s). By contrast, late/post-pubertal girls demonstrated earlier semitendinosus onset compared to both early/mid- (MD = 0.02, 95% CI = 0.03, 0.005 ms) and pre-pubertal girls (MD = 0.02, 95% CI = 0.04, 0.007 ms). No other between-group differences were found for peak A/P, vertical and TTP vertical tibial acceleration (p > 0.05). Subsequently, regression analysis revealed that EMG variables accounted for approximately 34% (R² = 0.34) of the variance in TTP A/P tibial acceleration. These findings highlight that neuromuscular recruitment patterns and kinetics differ across female pubertal development while running and should be further explored in the context of adolescent female musculoskeletal injuries.     

Association between interleukin-6 gene − 174 G/C polymorphism and the risk of coronary heart disease: A meta-analysis of 20 studies including 9619 cases and 10,919 controls

Interleukin-6 (IL-6) gene − 174 G/C polymorphism has been reported to be associated with coronary heart disease (CHD), but the results remain inconclusive. The present meta-analysis was therefore designed to clarify these controversies. This meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 20 studies including 9619 CHD cases and 10,919 controls were combined showing no evidence of association between IL-6 gene − 174 G/C polymorphism and CHD risk (for C/C + C/G vs. G/G: OR = 1.10, 95% CI = 0.99–1.22, p = 0.07; for C/C vs. C/G + G/G: OR = 1.08, 95% CI = 0.93–1.24, p = 0.33; for C/C vs. G/G: OR = 1.16, 95% CI = 0.97–1.39, p = 0.11; for C allele vs. G allele: OR = 1.10, 95% CI = 1.00–1.21, p = 0.06). Moreover, we also did not find significant association between IL-6 gene − 174 G/C polymorphism and myocardial infarction (MI) risk. However, in the subgroup analysis by ethnicity, significant association was found among Asians (for C/C + C/G vs. G/G: OR = 1.35, 95% CI = 1.05–1.63, p = 0.02). In summary, the present meta-analysis suggests that IL-6 gene − 174 G/C polymorphism is associated with increased CHD risk among Asians. However, due to the small subjects included in the subgroup analysis of Asians, the results should be interpreted with caution.     

Association of the macrophage migration inhibitory factor gene − 173G/C polymorphism with inflammatory bowel disease: A meta-analysis of 4296 subjects

A variety of epidemiologic studies have focused on the association between macrophage migration inhibitory factor (MIF) gene − 173G/C polymorphism and inflammatory bowel disease (IBD). However, results in different studies have been inconsistent. In order to derive a more precise estimation of the associations, we performed this meta-analysis and systematic searches of electronic databases PubMed and Web of Science (up to April 30, 2013). Based on our search criteria, a total of seven eligible studies concerning the MIF − 173G/C polymorphism and IBD risk were included in the final meta-analysis, comprising 2162 IBD cases and 2134 controls. Significant association was found between MIF − 173G/C polymorphism and the risk of IBD when all studies were pooled into the meta-analysis (for C allele vs. G allele: OR = 1.25, 95% CI = 1.12–1.41, p = 0.000; for C/C vs. G/G: OR = 1.71, 95% CI = 1.23–2.39, p = 0.002; for C/C + G/C vs. G/G: OR = 1.24, 95% CI = 1.09–1.42, p = 0.002; for C/C vs. G/C + G/G: OR = 1.67, 95% CI = 1.20–2.33, p = 0.002). Heterogeneity and publication bias did not exist in the overall comparisons. The present meta-analysis suggests an association between the MIF − 173G/C polymorphism and IBD risk. However, due to few studies and the selection bias existed in some studies, the results should be interpreted with caution.     

<Emphasis Type="Italic">FAS</Emphasis> −1,377 G/A polymorphism is associated with cancer susceptibility: evidence from 10,564 cases and 12,075 controls

Published data on the association between FAS −1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with AA variant genotype when all the eligible studies were pooled into the meta-analysis (for AA vs GG: OR = 1.19; 95% CI = 1.01–1.40; P _{heterogeneity} = 0.05; for recessive model: OR = 1.21; 95% CI = 1.04–1.41; P _{heterogeneity} = 0.05). In the subgroup analysis by ethnicity, borderline statistically significantly increased risks were found among Asians for recessive model (OR = 1.20; 95% CI = 1.00–1.45; P _{heterogeneity} = 0.01). In the subgroup analysis by population-based controls or hospital-based controls, statistically significantly increased risks were found among groups with population-based controls for AA versus GG (OR = 1.27; 95% CI = 1.02–1.58; P _{heterogeneity} = 0.05) and recessive model (OR = 1.25; 95% CI = 1.00–1.59; P _{heterogeneity} = 0.01). For breast cancer, borderline statistically significantly increased risks were found for AA versus GG (OR = 1.29; 95% CI = 1.00–1.67; P _{heterogeneity} = 0.41). In summary, this meta-analysis suggests that the FAS −1,377 G/A polymorphism is associated with cancer susceptibility. L. X. Qiu, J. Shi and H. Yuan contributed equally to this work and should be considered as co-first authors.     

Kanglaite injection plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 27 RCTs

BackgroundKanglaite injection (KLT) is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of advanced lung cancer.PurposeTo evaluate the combined effects of Kanglaite injection plus platinum-based chemotherapy (PBC) on patients with stage III/IV non-small cell lung cancer (NSCLC).Study designA systematic review and meta-analysis of randomized clinical trials (RCTs).Materials and methodsTwelve databases were searched from their inceptions until July 05, 2019. All the RCTs comparing the efficacy and safety of Kanglaite injection plus PBC versus PBC alone were selected. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis (TSA). Disease control rate (DCR) was defined as the primary endpoint, objective response rate (ORR), survival rate, quality of life (QOL), cellular immunity function, and toxicities were defined as the secondary endpoints.ResultsTwenty-seven RCTs recruiting 2,243 patients with stage III/IV NSCLC were included. The results showed that, compared with PBC alone, Kanglaite injection plus PBC improved DCR (RR = 1.20, 95% CI 1.15–1.26, p < 0.00001), ORR (RR = 1.45, 95% CI 1.31–1.60, p < 0.00001), 1-year survival rate (RR = 1.20, 95% CI 1.02–1.43, p = 0.03), QOL (RR = 1.32, 95% CI 1.25–1.40, p < 0.00001), CD4⁺ T cells (WMD = 4.86, 95% CI 4.00–5.73, p < 0.00001), CD4⁺/CD8⁺ ratio (WMD = 0.19, 95% CI 0.07–0.31, p < 0.002), and reduced severe toxicities by 59% (RR = 0.41, 95% CI 0.33–0.51, p < 0.00001). Most results were robust and the quality of evidence was from moderate to low.ConclusionsKanglaite injection in combination with PBC showed significantly higher efficacy than PBC alone in the treatment of stage III/IV NSCLC. Moreover, the combination therapy can improve cellular immunity and attenuate the severe toxicities caused by chemotherapy. However, high-quality RCTs are warranted to further assess the effects of the combined therapy.     

Association between ATM 5557G>A polymorphism and breast cancer risk: a meta-analysis

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83–1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58–1.03; for dominant model: OR = 1.04, 95% CI = 0.82–1.31; for recessive model: OR = 0.87, 95% CI = 0.69–1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38–3.47; for dominant model: OR = 2.15, 95% CI = 1.37–3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution.     

Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma

Published studies on the relationships between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and lung cancer risk. A total of 15 studies including 10,753 cases and 11,275 controls described C677T genotypes, among which 11 articles totalling 6,161 cases and 7,684 controls described A1298C genotypes, were also involved in this meta-analysis. Overall, no significantly elevated lung cancer risk was found in any genetic models when all studies were pooled. For C677T polymorphism: (TT vs. CC: OR = 1.17, 95% CI = 0.97–1.42; TC vs. CC: OR = 1.06, 95% CI = 0.94–1.20; dominant model: OR = 1.09, 95% CI = 0.96–1.24; and recessive model: OR = 1.08, 95% CI = 0.95–1.24); for A1298C polymorphism: (CC vs. AA: OR = 1.04, 95% CI = 0.91–1.19; AC vs. AA: OR = 0.98, 95% CI = 0.91–1.06; dominant model: OR = 0.99, 95% CI = 0.92–1.06; and recessive model: OR = 1.05, 95% CI = 0.92–1.20). In the subgroup analyses, the results showed that 677T varients could decrease lung cancer risk in female (OR = 0.63, 95% CI = 0.41–0.95, P-value = 0.03, 677CC as reference). No evidence of any associations of MTHFR A1298C polymorphism with lung cancer was found in overall or subgroup analyses. Our meta-analysis supports that the common polymorphisms of C677T and A1298C in MTHFR gene are not susceptibility gene for lung cancer from currently available evidence.