ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 , rs13181 , XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair , drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including  Among all primary lung cancers, non-small cell lung cancer (NSCLC) represents approximately 85% of cases. Chemotherapy remains the standard first-line treatment for almost 80% of NSCLC patients, of which platinum-based chemotherapy (PBC) is considered as the most efficacious option, especially for patients with an advanced stage of the disease3. Unfortunately, PBC efficacy varies markedly across individuals. Besides clinical and pathologic features, genetic variation is considered as an important factor to influence the treatment efficacy and prognosis.Lung cancer is a leading cause of cancer-associated death and substantially contributes to the heavy burden worldwide, with a dismal 5-year survival rate of 16.6%8. The accumulation of pharmacogenomics findings calls for a more comprehensive systematic review and meta-analysis to summarize the evidence and to identify the general genetic associations among reported results. Some meta-analyses have studied the influences of certain genes on treatment outcomes of NSCLC patients receiving PBC. However, these findings including original studies are not always consistent, and no systematic review and meta-analysis covering all tested polymorphisms has been performed thus far.For decades, we have witnessed a growing interest in the pharmacogenomics field, and a tremendous amount of epidemiological evidence that gene polymorphisms could give rise to varying drug response has emerged. Many studies have reported the association of genetic factors, including genes related to DNA repair pathway, drug influx and efflux, drug metabolism and detoxification, DNA synthesis, cell cycle control and apoptosis, with PBC response and prognosis of patientsERCC1, XPA, XPC, XPD, XPG, XRCC1, XRCC3, GSTP1, MTHFR, RRM1, MDR1 and CDA) have been studied in our work. The impacts of these genetic variants on PBC efficacy in NSCLC patients were assessed by evaluating the objective response ratio (ORR), progression-free survival (PFS), and overall survival (OS). We think this comprehensive meta-analysis with robust evidence would fill the gap in the pharmacogenomics of platinum in NSCLC patients.The aim of this work is to identify the effects of all eligible genes in clinical prognosis of NSCLC patients receiving platinum-based treatment. A total of 24 single nucleotide polymorphisms (SNPs) of 12 genes (9.We followed the principles proposed by the Human Genome Epidemiology Network (HuGeNet) HuGE Review Handbook of Genetic Association StudiesRelevant studies were searched in PubMed, Chinese National Knowledge Infrastructure (CNKI) and WANFANG databases. A two-step search strategy was implemented and last updated on January 31, 2016. First, the following three groups of keywords were used for searching in MEDLINE (via the PubMed gateway): platinum OR cisplatin OR carboplatin OR oxaliplatin OR nedaplatin, polymorphism OR SNP OR variant, NSCLC OR non-small cell lung cancer. Second, we used different combinations of the above terms for complementary searching. Besides, references cited in the retrieved papers were manually searched in case of missing relevant studies. Afterwards, we singled out the candidate genes that were eligible in our research, and the terms including a candidate gene’s official symbol and the three above-mentioned groups of keywords were used to perform a comprehensive search.The studies included in the meta-analysis had to meet all the following inclusion criteria: (i) cancer should be confirmed as NSCLC; (ii) treatment regimens were platinum-based chemotherapies; (iii) studies provided primary outcomes of interest including ORR, PFS or OS. Studies met any one of the exclusion criteria listed below were excluded in our analysis: (i) studies without indispensable data such as genotypes, overall response rate (ORR), overall survival (OS), or progression-free survival (PFS); (ii) studies with other types of lung cancer such as small cell lung cancer (SCLC) included; (iii) reviews, case reports, and meta-analyses. (iv) studies based on cell lines and animal experiment.All records were screened by three investigators independently  with disagreement resolved by discussion. The following information was extracted from each of the eligible studies: first author, publication year, sample size, ethnicity, age, gender, stages of tumor, chemotherapeutic agents, SNPs and genotyping methods, treatment outcomes.10. RR and the corresponding 95% CI were used to assess the association between each genetic variant and the response of NSCLC patients treated with PBC. The hazard ratios (HR) and corresponding 95% CI were determined to evaluate OS and PFS. Three genotypic models commonly used in genetic association synopses were applied in this meta-analysis: heterozygous or homozygous variant versus wild type, heterozygous variant versus wild type and homozygous variant versus wild type.We used the ORR as an indicator for PBC efficacy. Patients were classified into two groups: the responding group, which included complete and partial responders (CR and PR), and the non-responding group, which included subjects with stable or progressive diseases (SD and PD)2. Q tests with P > 0.10 were considered with statistical significance. I2 described the proportion of variation originating from heterogeneity rather than within-study error, whose value varied from 0 to 100 percent and indicated different heterogeneity degrees. Heterogeneity could be accepted when I2 < 50% . Sensitivity analysis and subgroup analysis were also applied to find the source of heterogeneity. Pooled RRs and HRs were calculated using the fixed-effects model when the heterogeneity was under the moderate degree or did not exist. Otherwise, the random-effects model was used. Moreover, the potential publication bias was assessed by statistical evaluation with Begg’s funnel plot and Egger’s linear regression test. The α level of significance was set at 0.05 unless noted otherwise.Between-study variance, also known as heterogeneity, was evaluated by the chi-square-based Q test based on chi- square as well as I11. The FPRP value was determined based on the P value, the prior probability for the association and statistical power. We set a stringent FPRP threshold of 0.20 and assigned a prior probability range of 0.1–0.001, and the statistical power was based on the ability to detect an OR of 1.5, with α equal to the observed p-value.In the end, we calculated the false positive report probability (FPRP) of statistically significant results to assess whether the findings were noteworthyAll statistical analyses were performed with STATA/SE.12.0  and R .After the process of selection, a total of 111 studies met the inclusion criteria and totally 18,196 NSCLC subjects (between the ages of 51 to 84) who accepted PBC were included in the final meta-analysis. More than 80% of these articles focused on the advanced NSCLC (in disease stages of III–IV). The process of selecting publications is presented in Fig. P < 0.05), with the remaining 112 being non-significant. For ORR, RR < 1 indicated that patients carrying the allele or genotype had a disadvantageous response, RR > 1 donated that the allele carriers had a favorable response. Pooled RR with 95% CI of individual SNPs identified as statistically associated with favorable responses to PBC were listed as follows: XRCC1 rs25487 , XRCC1 rs1799782 , XRCC3 rs861539 , XPA rs1800975 , GSTP1 rs1695 . Pooled RR with 95% CI of individual SNPs identified as statistically associated with unfavorable responses were presented below: ERCC1 rs3212986 , XPD rs13181 , XPD rs1799793 , MTHFR rs1801133 , MDR1 rs1045642 .As shown in Table ERCC1 rs11615 , ERCC1 rs3212986 , XPD rs13181 , and XPD rs1052555  might be related to a poorer OS, while XPG rs873601 , XPG rs2296147 , and XPD rs1799793  might be potentially related to a better OS. No significant association was identified in the remaining SNPs. As for PFS , and the T allele of XPD rs1052555 also indicated a poorer PFS .Statistically significant results with HR > 1 indicated that patients carrying the allele or genotype harbored a poorer OS or PFS, while with HR < 1 meant better OS or PFS of patients. As for OS Table , 52 meta2: 0 to 25%) and 14% (n = 25) presented moderate heterogeneity (I2: 25 to 50%), and large heterogeneity even extreme heterogeneity existed in other meta-analyses. Sensitivity analysis and subgroup analysis were also applied to find the source of heterogeneity. The clinical heterogeneity such as disease stages, different chemotherapy regimens might be the major reason for the large or extreme heterogeneity.A total of 54% (n = 97) of meta-analyses showed no heterogeneity , XRCC1 rs25487 (GA+AA vs. GG), XRCC1 rs1799782 (CT vs. CC) and XRCC3 rs861539  on the ORR had significant publication bias. There was also some publication bias in analysis of the effects of XRCC1 rs25487  on the OS. Three meta-analyses showed bias in the association of certain SNPs with PFS, including XPD rs13181 (AC+CC vs. AA), XPD rs1799793 (GA+AA vs. GG) and XRCC1 rs25487 (GA+AA vs. GG). More details were listed in Tables We used False positive findings regarding associations between genetic variants and diseases lead to a confounding effect. Here we assessed the FPRP to determine whether our finding was noteworthy. As shown in Table High-quality significant associations that emerged from the current meta-analysis were discussed below.ERCC1 rs3212986 (C8092A) variant was related to the treatment response to PBC, and A allele may have poorer response comparing with C allele in Asians . Only moderate between-study heterogeneity was observed (I2 = 29.2%), and with a low FPRP when prior probability level was set as 0.1, suggesting that A allele of ERCC1 rs3212986 might be specifically linked to the poorer response in Asians.Data showed that ERCC1 rs11615 (C354T) was associated with OS, and T allele carriers might have unfavorable OS with HR being 1.47 and corresponding 95% CI being 1.15–1.88, and with no heterogeneity and low FPRP when prior probability level was set as 0.1, but subgroup classification by ethnicity were not performed.XPD rs13181 (A2251C) mutation and OS due to insufficient raw data. We found that the variant C allele was remarkably associated with the adverse OS in overall NSCLC patients treated with PBC . There was no heterogeneity and publication bias in the meta-analysis, and FPRP was low with the prior probability level being 0.1. C allele was also related to poor PFS with low FPRP at the high prior probability levels . No heterogeneity with statistical significance was observed, but the P value for Egger’s test showed that there was some publication bias in the meta-analysis. These results indicated that C allele was a risk allele for the poor clinical prognosis of NSCLC patients.Only the dominant model was used to analyze the relation between XPD, we found that T allele was a risk allele and might be significantly associated with unfavorable OS . In the beginning, we included 4 articles in the meta-analysis and found that extreme heterogeneity and publication bias existed. After sensitivity analysis, we removed one article that was identified as the major source of heterogeneity, then I2 reduced to zero and no bias was observed from these data. The report had low FRPR with the prior probability level being 0.1 or 0.01. T allele was also related to poor PFS, and pooled HR was 1.97 and the 95% CI ranged from 1.38 to 2.83, though the report had low FPRP at high prior probability levels and no heterogeneity was observed. Further investigation with a larger sample size is needed to confirm the association between rs1052555 variant and prognosis of NSCLC patients.For other SNPs  of XPG rs2296147 (T242C) might be associated with NSCLC patients’ prognosis receiving platinum drugs. We found that T allele acted as a protective allele with the carriers having favorable OS , no heterogeneity and publication bias was detected, and the FPRP was low both at the high (0.1) and intermediate (0.01) prior probability levels. The strength of association needs to be further studied because of the small sample size of current meta-analysis.XRCC1 rs1799782 (C580T) polymorphisms and ORR, and results confirmed the positive response of patients carrying T allele to PBC with a low FPRP at the high (0.1) prior probability level, but large between-study heterogeneity existed in the three meta-analyses ; ; ).Three genetic models were used to analyze the association between XRCC1 rs861539 (C241T) was associated with the positive response of PBC treatment in Caucasian population, three genetic models had consistent results , no heterogeneity has been found. Begg’s test and Egger’s test revealed that some publication bias existed in the meta-analysis. However, Lower FRPR values suggested that the findings were statistically significant. Genetic variant of XRCC1 rs861539 was not associated with OS and PFS in the current meta-analysis.Results from subgroup meta-analysis sorted by ethnicity showed that T allele of MTHFR rs1801133 (C665T) might be related to the negative response, the report had low FPRP at the high (0.1) prior probability level, with pooled HR = 0.63, 95% CI = 0.44–0.89, I2 = 41.0% when comparing CT and CC genotypes. The other genetic models including TT vs. CC and CT+TT vs. CC didn’t show statistical significance.T allele of GSTP1 rs1695 (A313G), two genetic models showed consistent results about the association of the SNP with response , the same effects were also observed in the Asian group by subgroup analysis in model AG+GG vs. AA . However, we did not find a significant association in model AG vs. AA, low frequency of G allele and an insufficient sample size might be a major reason for it. We further assessed the FPRP value, and data showed low FPRP with probability level being 0.1. These results suggested that the G allele might play a protective role in the response of platinum-based treatment.For MDR1 rs1045642 (T3435C) polymorphism and treatment response in both overall and Asian groups in three comparison genetic models , and results are presented in Table There were statistically significant associations between EXCC1, XPD, XPG and XRCC1), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR).Genetic variants significantly associated with treatment outcomes of NSCLC patients receiving PBC had impacts on several biological pathways or certain physiological functions. As shown in Fig. In this study, we described the meta-analysis findings of associations between genetic polymorphisms and treatment outcomes of NSCLC patients receiving platinum drugs. Our study identified that 14 SNPs in 10 genes were statistically associated with clinical prognosis including treatment response, OS and PFS. We further calculated FPRPs of the statistically significant results and 23 results were identified with high-quality evidence Table .11. DNA repair pathways including nucleotide excision repair (NER) and base excision repair (BER) could timely repair the damaged DNA induced by platinum agents and thus lead to treatment failure122. ERCC1, XPA, XPC, XPD and XPG are important components of NER. Being consistent with the studies by Yang et al.123 and Xu et al.124, our results confirmed the association between T allele of ERCC1 rs11615 and shorter OS. In addition, we found that A allele of ERCC1 rs3212986 was a risk allele that could shorten the carriers’ OS and decrease the activity of platinum, while some previously published meta-analyses did not report this effect127. However, the association should be replicated in other subsequent studies. In the present meta-analysis, we firstly assessed the influence of ERCC1 rs2298881 variant, but no significant association was found. We studied four SNPs of XPD in this work and found that XPD rs13181, a common SNP of XPD, was closely related to reduced OS and PFS. For the other SNP (rs1052555) of XPD, we found that T allele was a risk allele and might significantly associate with unfavorable OS and PFS. This is the first meta-analysis to assess the XPD rs1052555 variant, and the robust association needs to be further confirmed by subsequent studies with larger sample sizes. For XPG, we found that rs2296147 might be related to patients’ OS, and T allele could indicate a favorable OS. The other three SNPs of XPG  showed no significant association with the ORR, OS and PFS. XRCC1 is a limiting factor in the base excision repair (BER) pathway. Our results and the previous studies confirmed the positive role of rs1799782 T allele in response to PBC130. For rs25487 of XRCC1, the statistically significant association between rs25487 polymorphism and ORR deserves to be further studied due to the high FRPR. XRCC3 is also important for DNA repair, Qiu et al. previously reported that XRCC3 rs861539 variation was related to good response of platinum treatment but not to survival, the same result was shown from the present meta-analysis. The MTHFR gene encodes an enzyme that is a central regulator for folate metabolism. It is suggested that MTHFR mutation was associated with increased risk of cardiovascular diseases and cancer131. We identified that the T allele was related to a negative response of PBC. MDR1 gene encodes for P-glycoprotein (P-gp), which plays a major role in the process of drug efflux and influx across the cell membrane132. We found that MDR1 rs1045642 variant was associated with ORR only in Asians, and published meta-analyses supported the association134. GST is a phase II metabolic enzyme involved in the platinum detoxification, mediated by glutathione (GSH) conjugation123. Increasing GSH content would decrease platinum-DNA binding and result in platinum resistance. GSTP1 gene was found to be associated with platinum treatment response, and our results indicated that T allele of GSTP1 rs1695 increased the ORR in NSCLL patients, but the association was only observed in Asians. A previous meta-analysis also reported the same effect as ours123.The anti-cancer activity of platinum agents mainly depends on the formation of DNA adducts which inhibit DNA replication, hinder cell division and induce cell apoptosisERCC1, XPD, XPG, XRCC1 and XRCC3) were involved in the efficacy of platinum treatment and clinical outcome of NSCLL patients. MDR1 and GSTP1, which were related to drug transportation and detoxification respectively, influenced the outcome of platinum treatment. Another potential key gene was MTHFR, which was involved in regulating folate metabolism and DNA synthesis and was correlated with platinum sensitivity.Great efforts have been made to identify the molecular predictive markers of platinum sensitivity. By further integrating our results according to genes biological functions, we found that the majority of polymorphisms of those genes significantly associated with treatment outcomes of platinum agents were involved in four biological pathways or physiological functions. According to the mechanism of platinum, DNA repair pathway may play a key role in the response of platinum therapy. Our results showed that the important components of DNA repair pathways  were used for this study, the other models including recessive model and allele comparison were not performed because of limited raw data. However, the models used in the study were commonly used in genetic analysis, and could in part decrease the type I error inflationIn conclusion, this collection of data might provide a useful platform for research and clinical healthy practice. Further work still needs to be done to pinpoint the use of these SNPs as prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.


The association of interleukin-10 rs1800896 polymorphism with head and neck cancer risk and its clinical stages has been investigated by many published studies, but the results remain inconsistent. Therefore, we conducted this meta-analysis for further investigation.Six case-control studies involving 1,781 head and neck cancer patients and 1,978 controls were yielded. The results indicated an association between rs1800896 polymorphism and increased head and neck risk . The subgroup analyses all obtained similar results with overall populations. The results of clinical stages yielded a non-significant association. No publication bias was detected.The PubMed and Chinese National Knowledge Infrastructure databases were searched up to December 27, 2016. Two authors independently selected studies, extracted and analyzed the data using the RevMan 5 software. Either a fixed effect or a random effect model was used to estimate pooled odds ratio and its 95% confidence intervals.We concluded that interleukin-10 rs1800896 polymorphism was significantly associated with head and neck cancer risk but not with the clinical stages thereof. Head and neck cancer (HNC) majorly includes cancers starting from oral cavity, pharynx, and larynx. The patients would suffer problems in communication or swallowing after surgerical treatment due to the special position; hence, it is important to seek risk factors of the disease for preventing its onset. Factors such as lack of toothbrushing , tobaccoThe interleukin-10 (IL-10) is a multifunctional immunosuppressant cytokine that is reported to be related to cancer onset and development . It is lThe initial search identified 77 publications and finally 6 studies , 20–22 cThe combined results from the included six studies showed that IL-10 rs1800896 polymorphism is associated with increased risk of HNC under all the five genetic models: [G vs. A: odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.30–2.04 ; GG vs. The source of controls of five studies was healthy volunteers , 20–22, The funnel plots of all five genetic models have well symmetry Figure , indicatThe pooled results of two studies , 21 indiSix case-control studies exploring the relationship between IL-10 rs1800896 polymorphism and risk of HNC were incorporated into the present meta-analysis. Of them, four studies reported a significant impact of IL-10 rs1800896 polymorphism on HNC risk , 20–21, HNC is a multifactorial disease –24, and By identifying these susceptible polymorphisms, population at high disease risk can be detected and prognosis of target disease can be predicted; it could be inferred from this meta-analysis that the population with rs1800896 polymorphism might have higher risk of developing HNC, and HNC patients at early stages with this mutation might be not likely to develop into advanced stages very quickly. Of course, this meta-analysis also indicated that IL-10 rs1800896 polymorphism could be used to identify and diagnose high risk population of HNC, but might be not valuable for judging the prognosis of HNC patients or the clinical stages.Compared with the two published meta-analyses –15, our Some limitations of our meta-analysis needed to be mentioned. The sample size was not large enough, especially in the analysis of clinical stages. As a result, the preciseness of true associations might be reduced, and subgroup analyses based on smoking status, gender, and ethnicity failed to be conducted due to lack of information. Second, the heterogeneity under some genetic models was significant, which also the case was found in the subgroup analyses Table  althoughIn summary, our meta-analysis indicated that IL-10 rs1800896 polymorphism might contribute to enhanced HNC susceptibility but had no apparent relationship with clinical stages of HNC. However, due to the limitations of our meta-analysis, more larger and well-designed prospective studies are needed to be performed to further confirm our findings.We included studies meeting all the following criteria: (1) the patients were diagnosed as HNC by pathological methods and the controls were healthy volunteers or HNC-free patients; (2) the exposure was IL-10 rs1800896 polymorphism and the study was a case-control or cohort study design; (3) the associations between IL-10 rs1800896 polymorphism and risk and/or clinical stages of HNC were explored; (4) complete information of necessary genotypes or other sufficient data to calculate them were reported. If the same institute published two or more publications, we treated them as independently ones and chose the more comprehensive one.A comprehensive literature search was performed in PubMed and CNKI  up to December 27, 2016. The following search term was used: (interleukin-10 OR IL-10) AND (polymorphism OR mutation OR variant OR variation) AND (carcinoma OR cancer OR tumor OR neoplasm) AND . Moreover, all listed references of included studies and recently reviews were also retrieved for potential articles. No language restriction was applied. P < 0.05 was considered as not conforming to HWE.Study selection and data extraction were performed by two authors independently and any possible discrepancy was resolved by discussion. The following data was extracted from each included study: surname of first author, year of publication, study design, country and ethnicity of study population, demographics, cancer sites, histopathologic types, smoking status, clinical stages, number of cases and controls, genotype distribution, source of controls, genotyping method, and Hardy-Weinberg equilibrium (HWE) for controls. The HWE was calculated if it was not reported and the level of Q statistic and I2 statistic [P ≥ 0.1 and I2 < 50% indicating acceptable heterogeneity, in which case the fixed effect model was used; otherwise, the random-effects model was used. The clinical stages were evaluated using the early stage (stages I and II) vs. advanced stage (stages III and IV). If the number of included studies was available, we conducted subgroup analyses based on the ethnicity, pathology types, and source of controls, cancer sites and smoking status. Publication bias was assessed by funnel plot [ORs and their 95% CIs were calculated to estimate the relationship under five genetic models of G vs. A, GG vs. AA, GA vs. AA, GA + GG vs. AA, and GG vs. AA + GA. Heterogeneity was assessed using the Cochran's tatistic –42 firstnel plot . All ananel plot , 17.


Controversial findings have been reported regarding to the effect of the transporter associated with antigen processing 1 (TAP1) polymorphisms exerted on the atopic diseases susceptibility. To gain a better understanding of the effects of TAP1 polymorphisms on the risk of atopic diseases, a retrospective study was carried out to evaluate the association of the most common TAP1 polymorphisms, rs1057141 and rs1135216, with the risk of atopic diseases. From studies published in PubMed, Embase, and Web of Science up to July 2017, ten eligible studies were selected for meta-analysis. The pooled results from rs1135216 polymorphism showed increased risk of atopic diseases in homozygote and recessive comparison. From the subgroup analysis by ethnicity, it was found that rs1135216 polymorphism contributed to atopic diseases susceptibility among Africans in all the five genetic models. Subgroup analysis by atopic types indicated significant association of TAP1 polymorphism rs1135216 with asthma in the allele, dominant and recessive models and with allergic rhinitis in the recessive model. As to rs1057141, increased risk of atopic disease in the allelic, dominant and heterozygous model was found in African population. Overall, this meta-analysis study demonstrated that rs1135216 polymorphism may contribute to atopic diseases susceptibility in Asians and Africans as assessed in this study. However, well designed large-scale case-control studies are needed to confirm such preliminary findings. Atopic diseases which include atopic dermatitis(AD), allergic rhinitis(AR), and asthma(AA) are closely related. Allergic rhinitis is often present in asthmatics and the incidence of asthma development in individuals suffering from allergic rhinitis is five times of those bearing no allergic rhinitis . It has It has been proposed that TAP gene may be responsible for atopic disease susceptibility. Polymorphisms in TAP1 may affect antigen recognition and presentation, potentially resulting in low expression or entirely absence of MHC-I at the cell surface, which could ultimately lead to an adverse immune response . StudiesBy following literature selection process as illustrated in Figure Meta-analysis results2 = 22.1%, Ph = 0.260) and Africans  in allelic comparisons , dominant  and heterozygous  model .AD, atopic dermatitis; AR, allergic rhinitis; AA, asthma; OR, odds ratio; CI, confidence interval; NA, not applicable; Bold values are statistically significant (P < 0.001) and homozygote comparison  in overall populations  but not in Asians  and Africans  in homozygous comparison , dominant  and heterozygous  models and AR in the recessive  and homozygous  models  and homozygote comparison (Pegger = 0.026)  and African  groups  Table . HoweverP < 0.05).AD, atopic dermatitis; AR, allergic rhinitis; AA, asthma; OR, odds ratio; CI, confidence interval; NA, not applicable; Bold values are statistically significant  were used as the source for identifying published investigations on the relationship between TAP1 polymorphism and atopic risk. Time was not limited for the search of the eligible literature. Keywords used for searching the literature include: ‘transporter associated with antigen processing 1’,‘TAP1’, ‘polymorphism’, ‘variant’, ‘genotype’, ‘allele’, ‘dermatitis’, ‘rhinitis’, and ‘asthma’. Besides, to identify further eligible articles, reference lists of all relevant articles were reviewed manually.Criteria used for selection of eligible studies include: (1) being a unrelated case-control design study; (2) include investigation of the relationship between TAP1 polymorphisms and atopic dermatitis, allergic rhinitis, and/or asthma; (3) including sufficient data to calculate the pooled ORs with 95% CI .The types of data extracted from the included studies are: first author, publication year, country, ethnicity, genotype methods, the number of cases and controls, distributions of genotypes and alleles in atopic patients and control subjects, and the probability value of HWE in control group. Data extraction was carried out independently by Liu and Chen who also performed study quality assessment. Disagreements were solved by discussion.Scoring system was established by incorporating traditional epidemiological considerations together with atopic genetic issues recommended by Thakkinstian to assess study quality . Six perP < 0.1 considered as significant. In the presence of heterogeneity among individual studies, estimation of pooled OR was conducted utilizing a random-effect model. Otherwise, a fixed-effect model was applied. The pooled OR was determined by Z-test, and OR with P < 0.05 was considered as significant [2 test, and significance was set at P < 0.05. Subgroup analysis by ethnicity and atopic types was performed to investigate possible causes of heterogeneity. Influence of individual study on the overall analysis outcome was assessed by sensitivity analysis, in which the results by stability was tested by excluding each study in sequence to examine their impact on the test of heterogeneity. To determine whether there existed publication bias, Funnel plots, Begg's test and Egger's test were applied. In the case of presence of publication bias, the trim and fill approach was applied to adjust the meta-analysis results by imputing data from presumed missing studies [Statistical analysis was performed with StataMP 14 . Five genetic models including the allelic (G versus A), dominant (AG+GG versus AA), recessive (GG versus AG+AA), homozygous (GG versus AA) and heterozygous (AG versus AA) models were adopted . The relnificant . To conf studies .


Femoral nerve blocks (FNB) can provide effective pain relief but result in quadriceps weakness with increased risk of falls following total knee arthroplasty (TKA). Adductor canal block (ACB) is a relatively new alternative providing pure sensory blockade with minimal effect on quadriceps strength. The meta-analysis was designed to evaluate whether ACB exhibited better outcomes with respect to quadriceps strength, pain control, ambulation ability, and complications. PubMed, Embase, Web of Science, Wan Fang, China National Knowledge Internet (CNKI) and the Cochrane Database were searched for RCTs comparing ACB with FNB after TKAs. Of 309 citations identified by our search strategy, 12 RCTs met the inclusion criteria. Compared to FNB, quadriceps maximum voluntary isometric contraction (MVIC) was significantly higher for ACB, which was consistent with the results regarding quadriceps strength assessed with manual muscle strength scale. Moreover, ACB had significantly higher risk of falling versus FNB. At any follow-up time, ACB was not inferior to FNB regarding pain control or opioid consumption, and showed better range of motion in comparison with FNB. ACB is superior to the FNB regarding sparing of quadriceps strength and faster knee function recovery. It provides pain relief and opioid consumption comparable to FNB and is associated with decreased risk of falls. Total knee arthroplasty (TKA) is regarded as an effective treatment for end-stage knee osteoarthritis146588910Adductor canal block (ACB) is a relatively new alternative for post-TKA pain management. Regional anesthesia is deposited within an adductor canal that can be easily visualized at the middle third of the thigh with use of ultrasonography. Consequently, ACB can be performed with a high success rate. Anatomical study of adductor canal showed that an adductor canal contained multiple afferent sensory nerves  but only a single efferent motor nerve  that potentially affected motor function1213et al. reported that ACB shows no superiority than FNB group regarding muscle strength and pain controlet al. demonstrated that ACB preserved greater quadriceps strength more than FNB with similar pain controlSeveral randomized controlled trials (RCT) have compared ACB to FNB. Many of these trials contained relatively small cohorts, and demonstrated inconsistent outcomes151617181921et al. (2015) conducted a recent meta-analysis of RCTs showing that ACB achieves better analgesic effects comparing with FNBSeveral more RCTs on this subject have been published without conclusive results202324Thus, we undertook a further meta-analysis to evaluate whether ACB is superior to FNB with respect to: (1) muscle strength; (2) pain score at rest or mobilization; (3) clinical outcomes; and (4) complications. We hypothesized that ACB results in less quadriceps motor impairment and incidence of falling, but provide similar analgesia and opioid intake.The systematic review and meta-analysis was in accordance with the PRISMA  guidelineshttp://www.prisma-statement.org). We systematically searched PubMed, Embase, Web of Science, Wan Fang, China National Knowledge Internet (CNKI), and the Cochrane Database from inception to April 10, 2016, with the search terms: “adductor canal block” OR “saphenous nerve block” OR “ACB” AND “femoral nerve block” OR “FNB”AND “total knee arthroplasty” OR “total knee replacement” OR “TKA” OR “TKR”. We supplemented our search with: (1) bibliographies from the earlier systematic reviews; (2) ongoing prospective RCTs from the ClinicalTrials.gov website; (3) references mining of eligible publications. There were no language or publication data restrictions on trial eligibility.We utilized a predetermined protocol in meta-analysis  of quadriceps and adductor, muscle strength, and visual analog scale (VAS) pain scores at rest or mobilization. The improvement in clinical knee function and complications was regarded as secondary outcomes. The secondary outcomes were complications , mobilization ability  and opioid rescue consumption.Corresponding authors of included studies were contacted via e-mail for relevant information if the available data were insufficient. Data in other forms  were converted to mean and standard deviation based on Cochrane Handbook. Discrepancies were resolved by consensus. When no consensus could be reached, a third reviewer cast the decisive vote.Two authors assessed the quality of included studies independently with use of Cochrane Collaboration tool (domain-based risk-of-bias tables)The quality of evidence for each finding was rated based on criteria established by the GRADE  group2 statistic. If significant (P < 0.1 or I2 > 50%), a random-effect model (REM) was used to estimate the overall effect sizes and a sensitivity analysis was carried out to investigate the potential sources of heterogeneity. Otherwise, fixed-effect model (FEM) was adopted. The Z test was used to evaluate the overall effect. In addition, publication bias was assessed by funnel plots.Review Manager 5.3 software was used for statistical analysis and a P-value < 0.05 was considered statistically significant. The odds ratios (OR) with 95% confidence intervals (CI) for ACB compared with FNB were calculated for dichotomous variables. If outcomes were measured in the same way between studies, we calculated mean differences (MD) and 95% CI for continuous variables. Heterogeneity was tested with use of the chi-squared test and IThe process of study selection was showed in 1516171819202324253132The risk-of-bias assessments were displayed below and in 151824These findings were considered as being of moderate to high quality through GRADE approach. The presence of studies with unclear risk of bias and one study with high risk of bias downgraded the quality of evidence (data not shown)151824P = 0.059) with moderate heterogeneity  with no heterogeneity  and 6–8 h18P = 0.08) with moderate heterogeneity  that ACB was superior to the FNB with regard to the change in quadriceps strength  were pooled from 10 trials151618192023253132Data on 486 primary TKAs (including 243 with ACB and 243 with FNB) from 8 trials15161819202425P = 0.08, TUG test, a validated ambulation test, was applied to assess mobilization ability postoperatively. Data on 272 primary TKAs (including 131 with ACB and 141 with FNB) were pooled from 5 trials16172023P = 0.08) and 72 h20P = 0.08). However, there were more post-TKA patients able to conduct TUG test in ACB, compared with those in FNB throughout the first 24 h  with no heterogeneity  was utilized to evaluate mobilization ability. Data on 403 primary TKAs (including 198 with ACB and 205 with FNB) from 6 trials1718242532P = 0.13) with moderate heterogeneity  were pooled from 3 trials1819P = 0.62) with moderate heterogeneity  from 5 trials16172325P = 0.66) with no heterogeneity  were pooled from 3 trials1619P = 0.18) with moderate heterogeneity  from 3 trials2531P = 0.79) and 72 h . In addition, the difference between groups was not significant within post-anesthesia 24 h , and no heterogeneity was identified  were pooled from 3 trials1920P = 0.003) with no heterogeneity  from 7 trials151620232532P = 0.98), pruritus (P = 0.69), and urinary retention (P = 0.63), respectively. No heterogeneity was identified 2 = 87%, P = 0.006) found no significant association between the two groups regarding quadriceps strength, which was different from this current meta-analysis with no heterogeneity.Quadriceps strength for both ACB and FNB groups was reduced compared with baseline. A previous study by Jaeger et al.We adopted three indicators of mobilization ability  to assess nerve blockade following TKA. In the current study, there were significantly more post-TKA patients able to conduct TUG test within 24 h in ACB group comparing with FNB group. However, no significant difference was identified between the groups at 48 h and 72 h. Interpretation of the outcomes must be made with caution due to the relatively small sample size and different dose of the analgesia. In addition, for those patients able to perform TUG test, we were not able to show a significant difference between the two groups in mobilization ability evaluated with the TUG test. Interestingly, these findings were inconsistent with the previous meta-analyses, and we believe our meta-analysis was more accurate and comprehensiveet al., it included two studies by Kwofie et al. and Jaeger et al. comparing quadriceps strength following ACB versus FNB in volunteers without TKAs, which did not meet the inclusion criteria of the meta-analysis 34et al. inappropriately combined data from RCTs and non-RCTs. Therefore, there is a need for subgroup analysis based on study design to evaluate the stability of the meta-analysis. Fifthly, the two studies did not use funnel plots to assess publication bias.There has been recent emphasis on whether ACB provides enough sensory coverage for TKA. Although the VAS pain scores were relatively lower in the two groups compared with baseline, no significant difference was observed in pain relief at any follow-up time between the groups, suggesting both ACB and FNB provided better analgesia without any statistical significance. It was established that small volume and low concentrations of local anesthetics substantially affected quadriceps strength and pain relief. Consequently, different doses of local anesthetics may have a minimal effect on the result. However, the optimal local anesthetic dose and concentration remain unclear and require further study. Interestingly, these findings were inconsistent with the previous meta-analyses26As for complications, there has been recent emphasis on risk of falls linked to peripheral nerve blocks. In our study, FNB increased the risk of falls post TKA, compared with ACB. Several studies have reported that FNB results in weakness of all four components of the quadriceps muscle increasing fall risks. On the contrary, ACB affects only vastus medialis, and thus greatly reduce the risk of falls173138Opioid consumption was no different in both groups, and the incidence of postoperative nausea and vomiting was low without significant difference. This is most likely due to effective blockade reduced opioid consumption and thus minimized associated side effects of nausea and vomiting. In addition, no significant difference was identified regarding other complications with no heterogeneity, such as pruritus and urinary retention.Our study had several strengths: Firstly, this is a comprehensive review of Level-I evidence on this topic with stricter inclusion criteria. . Secondly, this study included four new high-quality RCTs and contained a larger sample size than the previous meta-analysis, making possible a more robust conclusionThe limitations of this analysis include the relatively low number of patients for the ROM and patient satisfaction at different time points. In addition, another limitation is the lack of high-quality evidence in several outcomes. Furthermore, we found that heterogeneity may come from these risk factors, such as the age, gender, and dose and concentrations of local anesthetics. However, we cannot perform further analysis due to insufficient data on this topic. In addition, different anesthesia methods  may influence the postoperative pain scores.Although the overall quality of the evidence can be considered “average”, we objectively assessed the benefits and risk of ACB and FNB. Based on this meta-analysis of all currently published RCTs, the findings have important implications for the medical community, namely, that ACB is an effective alternative to provide less motor strength impairment and faster recovery but provides comparable level of pain relief with decreased risk of falls in comparison with the FNB.How to cite this article: Wang, D. et al. Adductor canal block versus femoral nerve block for total knee arthroplasty: a meta-analysis of randomized controlled trials. Sci. Rep.7, 40721; doi: 10.1038/srep40721 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD . The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample . When these data were stratified by apolipoprotein E (APOE) ε4 status, the observed association was confined to APOE ε4 non-carriers . Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD . To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within  APOE) was unequivocally demonstrated as established susceptibility gene for late-onset AD (LOAD) [APOE was not sufficient for the development of the disease. This suggest that there are additional risk loci influence the susceptibility of AD that remain to be discovered [HLA-DRB1 rs9271192 as new susceptibility loci in Caucasians [HLA-DRB1 gene in various ethnic groups might be different, further replication became the urgent task to be performed in other ethnic cohorts [HLA-DRB1 and LOAD to verify the above conclusions in the Northern Han Chinese population. Furthermore, there were other two large-scale studies investigated an association analysis between rs9271192 SNP within HLA-DRB1 and LOAD in Chinese, did not obtain a consistent conclusion in Chinese. So, we collected our data along with previously studies for meta-analysis to reach a more credible conclusion.Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease , 2. ReceD (LOAD) , 6, but scovered . In recescovered , 9. The ucasians . Since v cohorts . Hence, P = 0.067, P = 0.189, respectively) between AD and controls. Significantly lower Mini Mental State Examination (MMSE) score was found in LOAD patients compared to the controls (P < 0.001). As expected, the presence of the APOE ε4 allele was associated with of LOAD (P < 0.001) . And rs9271192 polymorphisms in HLA-DRB1 reached significant differences in the allele frequencies in the total sample (P = 0.04). Higher frequencies of the minor allele (C) were observed in patients with LOAD compared with control subjects (19.04% vs. 16.74%). When the genotype and allele distribution were stratified by the APOE ε4 allele status, we observed significant differences in the genotype frequencies in the APOE ε4 non-carriers (P = 0.002). In APOE ε4 allele carriers, the genotype and allele distribution of rs9271192 between LOAD patients and controls was no significantly different . Based on the observed prevalence of the minor alleles in controls, our sample size had greater than 90% power to detect a relative risk of 1.2 for rs9271192.Deviations from distributions of the polymorphisms were excluded by the HWE version 1.20 in both LOAD patients and controls. The allele and genotype frequencies of LOAD patients and controls in the total sample and after stratification for APOE ε4 allele status for the total sample; adjusted for age and gender for the subsets) . We further evaluated the association of rs9271192 with LOAD risk in patients with or without APOE ε4 allele using logistic regression in order to rule out confounding factors in the subsets. As indicated by Table APOE ε4 carriers, the C allele at rs9271192 increased LOAD risk in additive model and recessive model .We further investigated the distributions of the rs9271192 polymorphism in multivariate logistic regression analysis  Table . The res2 = 79.8%) in the Chinese subgroup  in the two subgroups .The initial search on computerized databases screened 19 articles. After 16 articles were excluded due to no correlation to rs9271192 or Alzheimer's disease, observational studies, editorials or reviews, 3 eligible articles were found . Moreover, we also found that non-APOE ε4 carriers with rs9271192 genotype CC had a significantly higher risk of LOAD than those with the genotype CA+AA . In contrast, APOE ε4 carriers with rs9271192 genotype CC did not have a higher risk than the other APOE ε4 carriers . The possible interpretation is that the genetic effect of HLA-DRB1 is predisposing factor to LOAD in the absence of the APOE ε4 allele, while APOE ε4 allele is the most susceptible genetic factor in APOE ε4 carriers [In our current study, there was statistically significant evidence for the carriers .2 = 79.8%) in the Chinese subgroup. There were two following researches made different conclusions in Chinese [HLA-DRB1 rs9271192 on AD was found to be associated with decreasing LOAD risk . The different sample sizes, many unknown demographic, clinical variables and possibility of false positives might attribute to the different results. When we carried out the sensitivity analysis and excluded the study of Jiao et al. [2 = 0.0%). Finally, the results of meta-analysis showed that the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD, and the result coincided with the recent large-scale GWAS and our study.Furthermore, the effects of some genetic variants confirmed by GWAS in various ethnic groups might be different, due to population-specific and some unknown gene-gene or gene-environment interactions. To avoid these possibly complicated reasons and further investigate these associations, meta-analysis was performed in Caucasians and Chinese. We found there was a high heterogeneity  and 1344 healthy control subjects  matched for gender and age. All the subjects in our study were unrelated Northern Han Chinese residents from Shandong province. The patients were assembled from the Department of Neurology of Qingdao Municipal Hospital and several other hospitals in Shandong. The subjects in case group were clinically diagnosed as “probable AD” by at least 2 neurologists, which according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and/or Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) . The AD HLA-DRB1 (rs9271192) was carried out by a patent-pending technology of SNP scan which was developed on double ligation and multiplex fluorescence PCR from Genesky Biotechnologies Inc. Randomly selected DNA samples from each genotype were sequenced to validate the genotyping by ligation detection reaction method, and the case status of study subjects was blind to the laboratory staff. Results of the ligation detection reaction method corresponded with the results of sequencing.Genomic DNA was extracted from the peripheral blood leukocytes by standard procedures using the Wizard genomic DNA purification kit . Genotyping for the 2 test. A binary logistic regression model, adjusted for age (age at examination for control subjects), gender and APOE ε4 status, was used to estimate ORs and the 95 %confidence interval (CI) for testing possible associations between SNPs and AD. We defined various genetic models as AA vs. (CA+CC) for dominant, CC vs. (CA + AA) for recessive, and CC vs. AA for additive. The statistical power was calculated by STPLAN 4.5 software.HWE version 1.20  was used to exclude deviations from Hardy–Weinberg equilibrium (HWE). Differences in the characteristics of the study subjects between the two groups were examined using the Student t test or the Chi-square test. Genotype and allele distributions were compared in the two groups by using the xHLA-DRB1 rs9271192 polymorphism and AD. The key search terms including HLA-DRB1, HLA-DRB5–DRB1, rs9271192, Alzheimer's disease, and AD, combined with Boolean operators as appropriate. There were no language restrictions in our research. The reference lists of relevant primary articles were the source of additional studies.We carried out a systematic literature search of MEDLINE, EMBASE and the Cochrane library for studies published in the period from January 1995 to January 2016 to investigate the association between the The adopted articles were in accord to the following criteria: (1) case–control studies design; (2) Patients were included if they met the NINCDS–ADRDA criteria for AD diagnosis; (3) data of the ORs with corresponding 95% CIs were available in the report or could be calculated. Reviews, editorials, articles without essential data, and papers focused on familial AD were eliminated. Additionally, we only selected the data from the most comprehensive report for the meta-analysis if there was more than one publication from the same population.Two reviewers cooperated to accomplish data abstraction which was blinded to the authors and journal. Discrepancies in the collected data were discussed with other team members or contact with original investigators. If consensus was not reached, a third reviewer decided the final result. Once data of the ORs with corresponding 95 % CIs could not extract directly, we sought them from the authors. We tried to seek the missing information and essential clarification from the original authors. According to the data of each qualified study, we extracted the ORs with corresponding 95 % CIs from logistic regression. The study quality was assessed with the Newcastle-Ottawa Quality Scale (NOS). Our studies were considered high-quality, with a score of at least seven points.HLA-DRB1 (rs9271192) and LOAD [2 estimates with evaluate the possible effect of study heterogeneity on the results . Our studies used Stata V.12.0 to perform all the meta-analyses.We pooled our data with the results from meta-analysis of 82501 individuals  and otheand LOAD , 17 by f


Many studies have reported harmful effects of red meat or processed meat on chronic diseases including cancer and diabetes, but epidemiological evidence for metabolic syndrome is limited and remains controversial. Therefore, we performed a meta-analysis of observational studies to assess the association between various meat consumption and risk of metabolic syndrome. The PubMed and ISI Web of Science databases were searched through June 2017, and further included unpublished results from Korea National Health and Nutrition Examination Survey 2012–2015, including 8387 Korean adults. Sixteen studies were suitable for meta-analysis, which included 19,579 cases among 76,111 participants. We used a random-effects model to calculate the pooled relative risks (RR) and 95% confidence intervals (CI). The pooled RR for metabolic syndrome of the highest versus lowest category of meat intake was 1.14  for total meat, 1.33  for red meat, 1.35  for processed meat, and 0.86  for white meat. All of these associations did not differ significantly by study design and adjustment factors. Our findings indicated that total, red, and processed meat intake is positively associated with metabolic syndrome, and white meat intake is inversely associated with metabolic syndrome. A significant increase in the prevalence of metabolic syndrome has been observed worldwide . MetabolAccumulating evidence from previous studies indicated that a high intake of red meat and processed meat could raise the risk of chronic diseases, including type 2 diabetes , CVD 7,,7,8, andTherefore, we conducted a systematic review and comprehensive meta-analysis to quantitatively evaluate the relationship between meat intake and metabolic syndrome. In addition, we analyzed the association using the data of Korea National Health and Nutrition Examination Survey (KNHANES) and included these new results in our meta-analysis.We searched the electronic databases (PubMed and ISI Web of Science) through June 2017 to identify eligible studies published in English as full-length articles. The search terms were the following: “ combined with (metabolic syndrome OR insulin resistant syndrome OR syndrome X).” The reference lists of retrieved articles or published reviews were also manually screened to search further relevant studies. ‘Red meat’ included red meat and processed red meat. ‘White meat’ included poultry. In the study conducted by Cocate et al. , fish waStudies were included in the current meta-analysis when they met the following criteria: (1) they were epidemiological studies; (2) the exposure of interest was meat consumption; (3) the outcome of interest was defined as prevalence or incidence of metabolic syndrome; and (4) they provided relative risks (RR) and 95% confidence intervals (CI). Studies targeting people with disease were excluded. Data were extracted according to the meta-analysis of observational studies in epidemiology (MOOSE) guidelines  by two iTo include all available data in the meta-analysis, we investigated the association between meat consumption and metabolic syndrome in KNHANES 2012–2015 and conducted a meta-analysis including these results. The KNHANES is a cross-sectional, nationally representative sample of the South Korean population that uses a multistage probability sampling design to represent the non-institutionalized civilian South Korean population. The KNHANES assessed the health and nutritional status of Koreans via 3 surveys including a health examination, a health interview, and a nutrition survey. The procedures of human subjects for KNHANES were approved by the Institutional Review Board of Korea Centers for Disease Control and Prevention, and informed consent was received from all subjects. Dietary consumption was assessed using the 112-item dish-based semi-quantitative food frequency questionnaires (FFQ) of KNHANES. Details of the study populations and methods are provided in the online-only Data Supplement.Q [2I statistics [p-value less than 0.05 was deemed statistically significant.In the present meta-analysis, odds ratios (ORs) and hazard ratios (HRs) were considered equivalent to RRs . The natQ  and I2 satistics . The subatistics  and Beggatistics . All staThe characteristics of study populations by meat consumption are present in Sixteen studies including 19,579 cases among 76,111 participants were suitable for meta-analysis  13,14,1,33,34,35p = 0.08, I2 = 41.9%)   . In a searisons) . p < 0.001, I2 = 83.2%) . By meat intake assessment, studies which assessed meat intake by grams showed a positive association , while studies which assessed meat intake by servings or frequencies showed the inverse association  (p = 0.002). There was no significant difference by study design or adjustment factors   . In the arisons) .p = 0.57, I2 = 0.0%)  . The sump = 0.78, I2 = 0.0%)   . In the arisons) . p = 0.72; Egger’s p = 0.90), red meat , processed meat , and white meat  intake.We found no evidence of publication bias for the meta-analysis of total meat  [The evidence of heterogeneity between studies was found in the meta-analysis of red meat intake and risk of metabolic syndrome. The possible reason for the observed heterogeneity was found in the subgroup analysis by geographic region. The results from the Asian population showed an inverse association between red meat intake and metabolic syndrome unlike the results from other populations. The observed heterogeneity in the analysis of red meat consumption disappeared after excluding studies targeting the Asian population ( = 0.31) ,35. More = 0.31) . Relativ = 0.31) .Several meta-analyses reported that a high intake of red and processed meat would raise the risk of diabetes ,37, CVD In our nationally representative study including 8387 Korean adults aged 19–64 years, the intake of red and processed meat was not significantly associated with the prevalence of metabolic syndrome. These non-significant associations are similar to previous results from Asian studies. A cross-sectional study on the Thai population reported a non-significant association between meat intake and the prevalence of metabolic syndrome in men  and women  in the analysis of the highest vs. lowest quartile of meat intake . A pooleSome potential mechanisms might explain a harmful effect of red and processed meat intake on metabolic syndrome. Red meat contains large amounts of total fat, saturated fat and haem-iron. Total and saturated fat might increase metabolic syndrome risk by obesity, hyperinsulinaemia and hyperglycemia ,44. IronTo the best of our knowledge, this is the first comprehensive meta-analysis to examine the relationship between total, red, processed and white meat consumption and the risk of metabolic syndrome. We conducted the analyses by types of meat. Most of the studies that were included in the meta-analysis were controlled for confounding factors including age, alcohol consumption, smoking, or physical activity. In addition, the relationships of total, white, red, and processed meat consumption and metabolic syndrome risk did not substantially differ by study design and adjustment factors, and we found no evidence of publication bias in all analyses. Despite these strengths, there are several limitations which should be considered. First, most of the studies that were included in our meta-analysis evaluated meat intake using FFQ, and thus, our results are susceptible to some degree of misclassification. However, the misclassification in the evaluation of exposure would more likely be non-differential, and the results would have biased toward the null. Second, a meta-analysis of observational studies cannot address problems of confounders that could be inherent in the original studies. Although most of the studies included in the meta-analysis controlled for other known risk factors including age, alcohol consumption, smoking or physical activity, residual confounding cannot be totally ruled out. People consuming more meat tended to have a low fruit and vegetable consumption. Some of the studies included in the meta-analysis controlled other food intake, but other studies did not. More well-designed studies that include various food consumption as an adjustment variable are required to confirm the association between meat consumption and the risk of metabolic syndrome. Third, because our study in Korean adults had a cross-sectional design, which assessed information of exposure and outcome simultaneously, the direction of causality cannot be inferred. However, we tried to eliminate a possible reverse causation bias by excluding both participants with a self-reported diagnosis of hypertension, diabetes, dyslipidemia, stroke, myocardial infarction, or cancer and those who were taking medications to control diabetes, hypertension, or dyslipidemia. Lastly, the results of the Korean adults were significant only in relation to the components of the metabolic syndrome such as hypertriglyceridemia, elevated blood pressure, and hyperglycemia.In conclusion, we observed that total, red, and processed meat consumption was associated with a high risk of metabolic syndrome, while white meat consumption was inversely associated with the risk of metabolic syndrome. White meat intake was inversely associated with the prevalence of hypertriglyceridemia and elevated blood pressure, and high processed meat intake was associated with the raised prevalence of hyperglycemia in Korean adults. Our findings suggest that the effect on health is different by the types of meat and also support current common dietary guidelines to decrease the intake of red and processed meat and increase the consumption of white meat. The results of this study need to be confirmed in well-designed prospective cohort studies and randomized controlled trials on a large population.


Purpose. Urothelial carcinoma-associated 1 (UCA1) has been reported to be overexpressed and correlated with progression in various cancers. However, the association between UCA1 expression and some clinicopathological features of digestive system malignancies, such as metastasis and survival, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of UCA1 in digestive system malignancies. Methods. Relevant literatures were searched in PubMed, Web of Science, Cochrane Library, and Embase databases updated to May 2016. Results. A total of 1089 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that digestive system malignancy patients with UCA1 overexpression were significantly more susceptible to developing lymph node metastasis (LNM)  and distant metastasis (DM)  and suffer from poor overall survival (OS)  and poor disease-free survival (DFS) . Conclusion. UCA1 overexpression was correlated with LNM, DM, poor OS, and poor DFS. UCA1 may serve as an indicator for metastasis and poor prognosis in digestive system malignancies. Digestive system malignancies have threatened human health seriously. According to the GLOBOCAN estimates, there were about 3.4 million new cases and 2.9 million deaths caused by digestive system malignancies in 2012 worldwide ) OR urothelial carcinoma-associated 1 [Title/Abstract]) OR CUDR [Title/Abstract]) OR cancer up-regulated drug resistant [Title/Abstract])) AND ((((cancer) OR carcinoma) OR tumor) OR neoplasma)) AND  OR prognosis) OR prognositic) OR progression) OR recurrence) OR outcome) OR metastasis) OR clinicopathological)". In addition, the references in retrieved articles were screened manually for potential relevant studies.The articles collected were considered eligible if they met the inclusion criteria: (1) articles were investigating the association of UCA1 with progression of digestive system malignancies; (2) the expression levels of UCA1 in primary cancerous tissues were measured; (3) patients were grouped according to the expression levels of UCA1; (4) related clinicopathological parameters were described. Exclusion criteria are the following: (1) duplicate publications; (2) reviews, letters, comments, and conference articles; (3) studies focusing on UCA1 in other types of cancers, rather than digestive system malignancies; (4) studies using cells lines or animals, rather than cancer patients; (5) studies without usable data. Regarding multiple publications from the same medical center, only the most recent or the most complete study was included in the meta-analysis.http://digitizer.sourceforge.net/) and calculated as described [Two investigators  extracted data from the eligible studies independently, according to the inclusion and exclusion criteria. For disagreements, a consensus was achieved by a third investigator (Wei Qiu). The following information was collected from each eligible study: first author, publication year, region of patients, cancer type, total number of patients, detecting method of UCA1 expression, cut-off value of grouping, number of patients in high/low UCA1 expression group, number of patients with LNM and DM in each group, follow-up time, study endpoint, survival analysis method (multivariate or univariate), and hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) or disease-free survival (DFS). When the HRs and their 95% CIs were given in the articles, these data were extracted directly. If the prognosis was plotted as Kaplan–Meier curve, data was digitized by the software Engauge Digitizer version 4.1  criteria . The NOSχ2-based Q test and I2 statistics were used. When heterogeneity was significant (I2 > 50% or P < 0.10 for χ2), a random effects model was used; otherwise, fixed effects model was adopted. The potential publication bias was evaluated using a “funnel plot" as well as Begg's and Egger's test.To assess the heterogeneity among the included studies, P values were two-sided, and P < 0.05 was considered statistically significant.The meta-analysis was performed through using Stata SE12.0 (Stata Corporation). All A total of 156 records were retrieved by searching the databases of PubMed, Web of Science, Cochrane Library, and Embase. After screening the title and abstract, 125 articles were excluded because they were either duplication or reviews or about other lncRNAs. For the thirty-one articles remaining, full text was assessed carefully and 21 were excluded for their insufficient data, or for they focused on the level of UCA1 from other cancers rather than digestive system malignancies. Finally, 10 articles comprising 1089 patients were identified as eligible and included in the present meta-analysis. The flow diagram was shown in The baseline characteristics of the included studies were summarized in I2 = 45.9% and P = 0.100), the fixed model was adopted. The pooled OR with 95% CI indicated that digestive system malignancy patients with high UCA1 level in tumor tissues were more susceptible to developing LNM   .I2 = 40.5% and P = 0.169), so the fixed model was applied to calculate the pooled OR and its 95% CI. The result showed that increased UCA1 expression was significantly correlated with DM   .Taken together, the results above showed that UCA1 overexpression was significantly correlated with LNM and DM in digestive system cancer patients, suggesting that UCA1 may serve as an indicator for metastasis of digestive system malignancies.I2 = 0%, P = 0.707). We found that high UCA1 level was significantly associated with poor OS  , the fixed model was used to assess the pooled HR and its 95% CI. We found that UCA1 overexpression was also significantly associated with poor OS   . On the = 0.000) .Results from the above analysis indicated that high expression of UCA1 was significantly correlated with poor OS in digestive system cancer patients, suggesting that UCA1 was an indicator of decreased survival rate in digestive system malignancies.I2 = 0.0%, P = 0.691, univariate analysis; I2 = 0.0%, P = 0.992, multivariate analysis), fixed-effect model was adopted to calculate the pooled HRs and their 95% CIs. The results showed that increased UCA1 expression was also significantly associated with poor DFS  , DM , or OS  or DFS . However, publication bias was found in the studies with OS . Besides, the funnel plots for LNM (In this meta-analysis, both Begg's and Egger's  for LNM , DM (Fig for LNM , OS from for LNM , and DFS for LNM  were larDigestive system malignancies constitute a major part of human cancers . Their rTo the best of our knowledge, this is the first meta-analysis to investigate the association of UCA1 expression with the metastasis and prognosis of digestive system malignancy patients. We included 10 studies with a total of 1089 patients. The pooled ORs with their 95% CIs showed that high UCA1 expression was significantly associated with LNM and DM, indicating that UCA1 was an indicator for metastasis of digestive system malignancies. Moreover, the pooled HRs with their 95% CIs showed that UCA1 overexpression was also significantly correlated with both poor OS and poor DFS, indicating that UCA1 overexpression may serve as an indicator of poor survival rate and high recurrence rate of digestive system malignancies, respectively. What is more, as the lncRNA can be secreted by cancer cells or released into the circulation from dead cancer cells, it has been reported that UCA1 level in plasma significantly decreased 14 days after surgery of colon cancer . To someNevertheless, there are several limitations in this meta-analysis. Firstly, most of the included studies were performed in the population from Asian countries rather than worldwide population; our results should be substantiated by additional studies in other races. Secondly, publication bias was observed in the studies with OS, which may be due to the fact that some studies were not included in this meta-analysis for their insufficient data or that some studies reported the correlation in one analytic method. Thirdly, the included studies were of small sample size as well as different cut-off value of UCA1 expression, which may generate errors by variation. Based on these limitations, the pooled ORs and HRs with their 95% CIs calculated in this meta-analysis may be just estimations.In conclusion, our meta-analysis showed that UCA1 overexpression was correlated with LNM, DM, poor OS, and poor DFS in digestive system malignancy patients. Therefore, UCA1 may serve as an indicator of metastasis and prognosis in digestive system malignancies.


ATM genetic polymorphisms and cancer risk in individuals with or without radiation exposure to determine whether there was a joint effect between the ATM gene and radiation exposure in carcinogenesis.We conducted two meta-analyses of ATM polymorphism investigated by more than 3 studies of radiation exposure, was eligible for the present study. The meta-analysis of 23333 individuals without radiation exposure from 24 studies showed no association between the rs1801516 polymorphism and cancer risk, without heterogeneity across studies. The meta-analysis of 3787 individuals with radiation exposure from 6 studies showed a significant association between the rs1801516 polymorphism and a decreased cancer risk, with heterogeneity across studies. There was a borderline-significant difference between the ORs of the two meta-analyses (P = 0.066), and the difference was significant when only Caucasians were included (P = 0.011).rs1801516, which was the only ATM genetic polymorphisms and cancer risk. Tests of interaction were used to compare differences between the ORs of the two meta-analyses.Publications were identified by searching PubMed, EMBASE, Web of Science, and CNKI databases. Odds ratios (ORs) were calculated to estimate the association between Our meta-analyses confirmed the presence of a gene-environment interaction between the rs1801516 polymorphism and radiation exposure in carcinogenesis, whereas no association was found between the rs1801516 polymorphism and cancer risk for individuals without radiation exposure. The heterogeneity observed in the meta-analysis of individuals with radiation exposure might be due to gene-ethnicity or gene-gene interactions. Further studies are needed to elucidate sources of the heterogeneity. The International Agency for Research on Cancer has confirmed that ionizing radiation is associated with an increased risk for a wide range of cancers, including breast cancer, thyroid cancer, and leukemia . The risATM) protein plays a central role in mediating the cellular response to radiation-induced DNA damage [ATM gene cause ataxia-telangiectasia, a recessive genetic disorder with a high incidence of cancer [ATM gene may alter the risk of carcinogenesis [ATM genetic polymorphisms with cancer risk. Some of the polymorphisms have been reported by more than 10 studies, such as rs1801516, IVS10-6T > G, rs1800057, rs1800054, rs1800056, rs1800058, and rs4986761. Although most of the findings on these polymorphisms were inconsistent, a meta-analysis of 11120 participants showed a significant association between the rs1800057 polymorphism and breast cancer risk [ATM gene and radiation exposure in the development of radiotherapy-induced adverse events [ATM genetic polymorphisms in carcinogenesis through gene–radiation interactions.The ataxia telangiectasia-mutated  in 5 studies [rs1801516 was the only exposure , 17–44, exposure –16 . There was little evidence of heterogeneity across studies (I2 ≤ 29.1%). Subgroup analyses were conducted in order to check whether the features of the included studies affected the results of this meta-analysis. For each genetic model, there was little variation in the effect sizes according to cancer site, ethnicity, study quality, and study size. Figures This meta-analysis included 24 studies with 9858 cases and 13475 controls , 22–44 , with high between study heterogeneity   [2 = 66.9%, P = 0.017), indicating that other factors might contribute to the heterogeneity. Table P = 0.005), whereas no association was shown among other subgroups. In addition, there was obvious evidence of heterogeneity in all subgroups (I2 ranged 66.9% to 81.8%), suggesting that the examined factors had a minimal influence on the variation of the estimates.To include all 6 studies for a summary OR estimate, the meta-analysis could only be conducted under the dominant model. The result showed a significant association between the rs1801516 polymorphism and a decreased risk of radiation-induced cancer . The difference was statistically significant when only Caucasians were included .The effect estimates for individuals in the absence and presence of radiation exposure were compared to determine the relationship of the interaction (synergistic or antagonistic) between radiation exposure and the rs1801516 polymorphism in carcinogenesis. Figure ATM gene and radiation exposure in carcinogenesis. rs1801516, which was the only ATM genetic polymorphism investigated by more than 3 studies, was eligible for the present study. Our meta-analyses showed that the rs1801516 polymorphism interacted with radiation exposure, resulting in a synergistic effect in carcinogenesis. In addition, we showed convincing evidence of no association between the rs1801516 polymorphism and cancer risk for individuals in the absence of radiation exposure.This work represents the first comprehensive assessment of the literature on the gene-environment interaction for polymorphisms in the The present meta-analysis of 23333 participants in the absence of radiation exposure had a very large sample size, and was able to provide convincing evidence of no association between the rs1801516 polymorphism and cancer risk. Up to now, 5 meta-analyses have been performed for the role of the rs1801516 polymorphism on cancer risk: 4 on breast cancer –48 and 1Our meta-analysis of 3787 participants in the presence of radiation exposure provided evidence of an association between the rs1801516 polymorphism and a decreased cancer risk for individuals who exposed to radiation. This meta-analysis included 6 studies across two ethnicities: 1 study in Polynesians and 5 studies in Caucasions. The natures of the two populations are different: the Polynesians are geographically isolated from the rest of the world, and have a significant variation in allele frequencies  as compared to the Caucasians (MAF in Caucasians = 0.19) , 15). InATM rs1801516 polymorphism is a polymorphic G-to-A transition at nucleotide 5557 of exon 39, resulting in a change from aspartic acid to asparagine at amino acid position 1853 of the protein [In vitro data showed that human fibroblasts carrying the minor alleles of the rs1801516 polymorphism increased cellular radiosensitivity compared with those carrying the major alleles [ATM gene, including the rs1801516 polymorphism, were reported to be associated with a decreased ATM expression and a reduced capacity of DNA damage recognition [ATM gene with BRCA1 has been reported [The  protein . In vitr alleles . Some vaognition , 53. Basreported , 52. TheATM variants on secondary breast cancer risk after treatment of primary breast cancer [Our study has a number of possible limitations. 1) Due to fewer than 10 studies in the meta-analysis of individuals with radiation exposure, the publication bias was not tested by the funnel plot, for this method could not obtain enough power in the case . Howevert cancer . In thist cancer . Becauset cancer , and shot cancer .ATM rs1801516 genotype and radiation exposure in carcinogenesis: there was convincing evidence of no association between the rs1801516 polymorphism and cancer risk of individuals in the absence of radiation exposure; there was evidence of a gene-environment interaction between the rs1801516 polymorphism and radiation exposure in carcinogenesis, and the heterogeneity observed across studies might be due to gender-ethnicity or gene-gene interactions. Further studies are needed to elucidate sources of the heterogeneity.In conclusion, the present study gave a clear picture of gene-environment interaction for the Our meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines .To be eligible for inclusion in our meta-analyses, a study had to meet all the following criteria: (1) it should be a case-control, cross-sectional, or cohort study in humans; (2) it can be published in any language, but it must be a full-text paper in an international peer-reviewed journal before December 31, 2015; (3) there was no restriction on cancer type, but it must report adequate information on genotype frequencies to estimate ORs for the cancer type. Case reports, editorials, meta-analyses, and review articles were excluded.A systematic literature search was conducted in Electronic databases, including PubMed, Web of Science, EMBASE, and Chinese National Knowledge Infrastructure , before December 31, 2015. We used the keywords: “(atm OR ataxia telangiectasia mutated) AND (polymorphism* OR variant* OR mutant* OR genotype*)”, in the searching process. This search yielded 3816 articles.ATM genetic polymorphisms and cancer risk in individuals in the presence of radiation exposure. After screened by title, abstract, or full text if necessary, we identified 6 articles including 17 polymorphisms. References from the relevant articles or reviews were also searched for additional studies. This search yielded no extra articles. Finally, we found that rs1801516 was the only ATM polymorphism investigated by more than 3 articles. Second, we collected articles on the association between the rs1801516 polymorphism and cancer risk in individuals in the absence of radiation exposure. We included all surrogates of the rs1801516 polymorphism, including rs52821794, rs60879649, rs17503060 (http://www.ncbi.nlm.nih.gov/snp/), and rs4988023 [To achieve adequate statistical power for the meta-analysis on gene-environment interactions in carcinogenesis, eligible polymorphisms were those reported by more than three data sources of radiation exposure. For this purpose, we employed a two-stage screen strategy Figure . First, s4988023 . Our seas4988023 , 62. If s4988023 . FinallyTwo authors independently extracted data based on a standardized form. The following information was collected from each study: first author, year of publication, country of origin, ethnicity, family history of cases , MAF in controls, controls in HWE, cancer site, and number of genotyped cases and controls. Ethnicity was classified as African-American, Amerindian, Asian, Caucasian, or others based on the ethnicity of at least 80% of the study population . When a Two authors independently evaluated the quality of each study, with discrepancies resolved during a consensus meeting. We performed two types of quality assessments. The first one was the assessment of methodological errors. Deviation from HWE in controls is an indication of a genotyping error or selection bias , 65, andTo clarify whether there was a joint effect between the rs1801516 polymorphism and radiation exposure in carcinogenesis, we performed three steps: 1). meta-analysis of the rs1801516 polymorphism and cancer risk in individuals in the presence of radiation exposure; 2). meta-analysis of the rs1801516 polymorphism and cancer risk in individuals in the absence of radiation exposure; 3). comparison of the differences in the effect estimates of the rs1801516 polymorphism on cancer risk between the two groups.Subgroup meta-analyses were conducted based on pre-specified interests, including cancer site, ethnicity, familial cancer history, study quality, sample size, and HWE in controls. The criteria for a subgroup analysis required at least 3 studies. We aimed at determining whether the result of the overall meta-analysis was stable or dependent on some features of the included studies. Sensitivity analysis was conducted by excluding 1 study at a time and analyzing the remaining ones to explore whether the result was influenced by a particular study.2 statistic. We used the random effects model  heterozygous model (AG versus GG), (2) homozygous model (AA versus GG), (3) dominant model (AA+AG versus GG), and (4) recessive model (AA versus AG+GG). The statistical significance of the ORs was evaluated by using the Z test. In case of zero cells, an appropriate continuity correction  was implemented . Betweens method ) to calcn et al.  was usedn et al.  and Beggn et al. . To asse


TGF‐β1) polymorphism was associated with radiation pneumonitis (RP) susceptibility, but their results have been inconsistent. The PubMed and CNKI were searched for case‐control studies published up to Januray 01, 2016 was Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta‐analysis, we assessed eight publications involving 368 radiation pneumonitis cases and 855 controls of the association between TGF‐β1 T869C (rs1982073) and G915C (rs1800471) polymorphism and RP susceptibility. Our analysis suggested that TGF‐β1 T869C rs1982073 polymorphism was associated with lower RP risk for CT combined CC versus TT model . However, for the G915C rs1800471 polymorphism, no association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model . These results from the meta‐analysis suggest that T869C rs1982073 polymorphism of TGF‐β1 may be associated with RP risk, and there may be no association between G915C polymorphism and RP risk.Transforming growth factor beta 1( Lung cancer remains the deadliest cancer worldwide despite improvements in diagnostic and therapeutic techniques Radiation pneumonitis (RP) is a dose‐limiting factor for radiotherapy and have a major influence on patients prognosis and life quality, which occurs in 5–15% of people who go through radiation therapy for lung cancer. Although many factors can influence the severity of reaction to radiotherapy, a large part of interpatient variability attribute to the individual differences in radio‐sensitivity, which was assumed to be determined by genetic variations among patients TGF‐β1) signalling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. TGF‐β1 gene is one of the most extensively studied cytokines in the development of tissue fibrosis in response to irradiation and TGF‐β1 signalling is an important modulator of the inflammatory response TGF‐β1 is a major regulator of radiation‐induced lung injury Transforming growth factor beta 1  or G915C (rs1800471) polymorphism and RP risk, (2) case–control studies, and (3) supply the number of individual genotypes for TGF‐β1 T869C (rs1982073) or G915C (rs1800471) in RP cases and controls, respectively. Major reasons for the exclusion of studies were as follows:(i) duplicate data, (ii) abstract, comment, review and editorial and (iii) no sufficient data were reported.For inclusion in this meta‐analysis, the identified articles had to provide information on the following: (1) evaluating the Information was carefully extracted from all eligible publications independently by two authors according to the inclusion criteria listed above. The following data were collected from each study: first author's surname, year of publication, ethnicity, total numbers of cases and controls, and numbers of cases and controls with the wild‐type genotypes, the genotypes of homozygote and allele carriers, respectively. If data from any of the above categories were not reported in the primary study, items were treated as ‘not applicable’. Different ethnicity descents were categorized as Asian, and Caucasian. For studies with inadequate information, authors of those studies were contacted for further information by E‐mail if possible.TGF‐β1 T869C (rs1982073) or G915C (rs1800471) polymorphisms and RP risk. The pooled ORs for the risk associated with the genotypes of homozygote and allele carriers with the wild‐type genotypes were calculated. Heterogeneity assumption was checked by the chi‐square‐based Q‐test P value greater than 0.10 for the Q‐test indicates a lack of heterogeneity among studies, so the pooled OR estimate of the each study was calculated by the fixed‐effects model (the Mantel–Haenszel method) t‐test suggested by Egger  OR (odds ratio) with 95% CI was used to assess the strength of association between the  G915C rs00471 pol T869C rs82073 or A total of eight publications involving 368 radiation pneumonitis cases and 855 controls met the inclusion criteria and were ultimately analysed –control studies with 339 cases and 714 controls were included for association between TGF‐b1 T869C (rs1982073) polymorphism and RP risk. The evaluations of the association of TGF‐b1 T869C polymorphism with RP risk are shown in Figure versus TT model . However, for the G915C (rs1800471) polymorphism, 7 studies with 274 cases and 710 controls were included eventually. No association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model . The funnel plots for publication bias . The funnel plots for publication bias  polymorphism showed that the Egger test was not significant  and G915C (rs1800471) polymorphisms of TGF‐β1 on RP susceptibility in lung cancer patients; however, the results remain conflicting rather than conclusive. Wang et al. TGF‐869C/T polymorphism was a risk factor of RP. Though that results were consistent with ours, only five studies were included in the meta‐analysis, while our study included eight studies and focused two genotypes of TGF‐β1. We have improved upon that previous meta‐analysis by including more recent related studies and by generally using a more comprehensive search strategy. We also explored heterogeneity and potential publication bias in accordance with published guidelines. In this meta‐analysis, we found that TGF‐β1 T869C (rs1982073) polymorphism may be associated with RP susceptibility, and there may be no association between G915C (rs1800471) polymorphism and RP susceptibility.In recent years, several molecular epidemiological studies have been conducted to evaluate the role of polymorphisms in the TGF‐β1T869C (rs1982073) polymorphism was associated with an increased RP susceptibility, while the TGF‐β1 G915C (rs1800471) was not associated with RP susceptibility when all the studies were pooled. These results implied that genetic factors may have played a greater role in influencing individual patient susceptibility, suggesting the possibility of using these biomarkers as predictive factors. In additional, future understanding of the combined effect of these polymorphisms on patient response to radiotherapy may shed some light on the predictive value of these genetic factors.The results of combined analyses suggested that the Some limitations of this meta‐analysis should be acknowledged. Firstly, we did not perform subgroup analysis by the pathological types of lung cancer due to limited data in primary studies. Because of different pathological types, subgroup analysis should be performed. However, some study in this meta‐analysis did not report separate genotype frequency for each pathological type of lung cancer, which prevented us to perform this subgroup analysis. Secondly, only published studies were included in this meta‐analysis. The presence of publication bias indicates that non‐significant or negative findings may be unpublished. Thirdly, the radiotherapy parameters, including total dose, dose per fraction, field size, irradiation volume and depth of prescription point, were not identical. The majority of the treatment protocols in the included studies were based on multimodality treatment that is an important potential confounding factor aggravating the adverse effects, particularly when adjuvant or concurrent chemotherapy was involved. Lastly, our results were based on unadjusted estimates, while a more precise analysis should be conducted if individual data were available, which would allow for the adjustment by other covariates including age, family history, environmental factors and lifestyle.TGF‐β1 T869C (rs1982073) polymorphism may be associated with RP risk. In addition, it is necessary to conduct large trials using standardized unbiased methods, homogeneous lung cancer patients and well‐matched controls, with the assessors blinded to the data. These patients might benefit from individual radiotherapy regimens and early intervention for adverse effects accordingly.In conclusion, this meta‐analysis suggests that The authors confirm that there are no conflicts of interest.