Association of ERCC gene polymorphism with osteosarcoma risk

BackgroundThe relationship between ERCC gene polymorphism and osteosarcoma risk / overall survival of osteosarcoma is still conflicting, and this meta-analysis was performed to assess these associations.Material and methodsThe association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method.ResultsFour studies were included for the association of ERCC gene polymorphism with osteosarcoma risk, and nine studies were recruited into this meta-analysis for the relationship between ERCC gene polymorphism and overall survival of osteosarcoma. The meta-analysis indicated that ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (A>G) gene polymorphism, ERCC2 rs13181 (Lys751Gln) gene polymorphism were not associated with osteosarcoma risk. ERCC1 rs2298881 (C>A) gene polymorphism, ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (Asp312Asn) gene polymorphism were not associated with overall survival of osteosarcoma. Interestingly, ERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma, but AA genotype not (A allele: OR = 0.78, 95% CI: 0.65–0.93, P = 0.007; GG genotype: OR = 1.32, 95% CI: 1.05–1.65, P = 0.02; AA genotype: OR = 0.69, 95% CI: 0.45–1.04, P = 0.08).ConclusionERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma.     

Association of STAT4 gene rs7574865G > T polymorphism with ulcerative colitis risk: evidence from 1532 cases and 3786 controls

Introduction

Several studies have reported the relationship between the STAT4 rs7574865G > T polymorphism as a susceptibility factor to ulcerative colitis (UC). However, the results have been controversial. Therefore, we conducted this meta-analysis to obtain the most reliable estimate of the association.

Material and methods

PubMed, Embase and Web of Science databases were searched. Crude odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled to assess the strength of the association between the STAT4 rs7574865G > T polymorphism and risk of UC. A total of five eligible studies including 1532 cases and 3786 controls based on the search criteria were involved in this meta-analysis.

Results

We observed that the STAT4 rs7574865G > T polymorphism was significantly correlated with UC risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.13, 95% CI = 1.02–1.25; the heterozygote codominant model: OR = 1.22, 95% CI = 1.04–1.43; the dominant model: OR = 1.25, 95% CI = 1.07–1.45). In the stratified analysis by ethnicity, significant associations were observed in Spanish for the allele contrast model (OR = 1.20; 95% CI = 1.04–1.39), for the homozygote codominant model (OR = 1.57; 95% CI = 1.07–2.31), for the dominant model (OR = 1.20; 95% CI = 1.01–1.43), and for the recessive model (OR = 1.50; 95% CI = 1.03–2.19).

Conclusions

This meta-analysis suggests that the STAT4 rs7574865G > T polymorphism is a low-penetrant risk factor for UC, especially in Spanish.     

The association between interleukin-1β gene polymorphisms and the risk of breast cancer: a systematic review and meta-analysis

IntroductionIt is reported that there is a close association between interleukin-1β (IL-1β) gene polymorphisms and breast cancer risk. However, the results remain controversial.Material and methodsEligible published articles were searched in PubMed, Embase, and Web of Science databases up to June 2018. Odds ratios with 95% confidence intervals were used to identify potential links between IL-1β genetic polymorphisms and the risk of breast cancer.ResultsFrom our results, we found that three common polymorphisms in IL-1β (rs16944, rs1143634, rs1143627) had no significant associations with breast cancer risk in all genetic models. Based on the analysis from ethnic subgroups, there was a higher risk of breast cancer for rs16944 polymorphism in the recessive model and heterozygous model among Asians (TT vs. CC+CT: 1.229, 95% CI: 1.063–1.422, p = 0.005; TT vs. CT: 1.211, 95% CI: 1.057–1.388, p = 0.006). For the rs1143627 polymorphism, a significantly decreased breast cancer risk was observed in the dominant model only in Asians (CT+TT vs. CC: OR = 0.944, 95% CI: 0.897–0.994, p = 0.027). After stratifying patients according to the menopausal state, we found that polymorphism of rs1143627 correlated with reduced breast cancer risk among post-menopausal women in three genotype models: allele, recessive model and homozygous model (T vs C: 0.859, 95% CI: 0.753–0.98, p = 0.024; TT vs. CC+CT: 0.727, 95% CI: 0.576–0.918, p = 0.007; TT vs. CC: 0.743, 95% CI: 0.626–0.882, p = 0.001). As for other analyses with reference to source of controls and genotyping methods, no significant association between IL-1β polymorphism and breast cancer risk was demonstrated.ConclusionsThe rs16944 and rs1143627 polymorphisms are significantly associated with the risk of breast cancer only in Asian people and in post-menopausal women respectively.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.     

Association between the Interleukin-10 -1082 G/A polymorphism and risk of hepatocellular carcinoma

BackgroundInconsistent results have been reported from studies investigating the relationship of the interleukin-10 (IL-10) -1082 G/A polymorphism and the susceptibility of hepatocellular carcinoma (HCC). Therefore, a thorough literature review of relatedstudies was performed in this meta-analysis to examine the association of the interleukin-10(IL-10) -1082 G/A polymorphism with HCC susceptibility.MethodsElectronic databases were searched for literature on the relationship between interleukin-10(IL-10) -1082 G/A polymorphism and the risk of HCC in accordance with the inclusion and exclusion criteria. The selected studies were analyzed using the Stata 12.0 software. Finally, the strength of the associations was evaluated using the odds ratio (OR) and 95% confidence intervals (95% CI).ResultsA total of six case-control studies were enrolled into the current meta-analysis, which included a total of 911 patients and 1889 control subjects. Our data revealed no association between the IL-10 -1082 G/A polymorphism and the risk of HCC (GG vs AA:OR=0.84, 95%CI=0.57–1.25; AG vs AA:OR=0.85, 95%CI=0.70–1.05; Dominant model: OR=0.85, 95%CI=0.70–1.03; and Recessive model: OR=0.92, 95%CI = 0.64–1.32). Similarly, no association was found in sub-group analysis based on ethnicity.ConclusionThe results of our study suggest no association between IL-10 -1082 G/A polymorphism and the risk of HCC.     

Impacts of CD152 polymorphisms on cervical cancer susceptibility

AimThe objective of this study was to discuss the effect of CD152 polymorphisms rs231775, rs3087243 and rs5742909 on the susceptibility to cervical cancer.MethodsThe databases of PubMed, EMBASE, Cochrane Library, ISI Web of Science, Google Scholar Web, CNKI and Wanfang were searched for eligible studies. Chi-square-based Q test examined heterogeneity between included studies, and when P_{heterogeneity} was less than 0.05, random-effect model was used to calculate odds ratios (ORs) with their 95 % confidence intervals (95 % CIs); or else, fixed-effect model was selected. Sensitivity analysis was implemented to determine the stability of final results through removing enrolled studies one at a time and then re-obtaining overall estimates. Publication bias among included studies was checked employing Begg’s funnel plot and Egger’s test.ResultsCD152 polymorphism rs231775 decreased cervical cancer risk in total analysis under the genetic models of GG vs. AA, GG vs. AA + AG and G vs. A (OR = 0.73, 95 % CI = 0.59–0.91; OR = 0.78, 95 % CI = 0.65–0.94; OR = 0.92, 95 % CI = 0.87–0.98), and so did the polymorphism rs3087243 in total analysis under the comparisons of AA vs. GG, AA + GA vs. GG, AA vs. GG + GA, A vs. G and GA vs. GG (OR = 0.51, 95 % CI = 0.42–0.60; OR = 0.71, 95 % CI = 0.62–0.82; OR = 0.57, 95 % CI = 0.50–0.66; OR = 0.70, 95 % CI = 0.64–0.77; OR = 0.83, 95 % CI = 0.72–0.97). Besides, the polymorphism rs5742909 elevated the disease onset in total analysis under the contrasts of TT vs. CC, TT + CT vs. CC, TT vs. CC + CT, T vs. C and CT vs. CC (OR = 2.66, 95 % CI = 1.75–4.04; OR = 1.54, 95 % CI = 1.24–1.91; OR = 2.13, 95 % CI = 1.12–4.03; OR = 1.44, 95 % CI = 1.17–1.78; OR = 1.49, 95 % CI = 1.22–1.83).ConclusionCD152 polymorphisms rs231775 and rs3087243 significantly decrease the risk of cervical cancer, while rs5742909 may increase the disease risk.     

IFN-γ +874 A>T (rs2430561) gene polymorphism and risk of pulmonary tuberculosis: a meta-analysis

IntroductionThe role of interferon gamma (IFN-γ) +874 A>T (rs2430561) gene polymorphism has been evaluated in different ethnicities with pulmonary tuberculosis (PTB) infection, and inconsistent results have been reported. In this study, a meta-analysis was performed to determine the precise association between IFN-γ +874 A>T gene polymorphism and PTB susceptibility.Material and methodsA total of 21 studies comprising 4281 confirmed PTB cases and 5186 healthy controls were included in this meta-analysis by searching the PubMed (Medline), EMBASE, and Google Scholar web-databases.ResultsWe observed reduced risk of PTB in allelic contrast (T vs. A: p = 0.001; OR = 0.818, 95% CI: 0.723–0.926), homozygous (TT vs. AA: p = 0.017; OR = 0.715, 95% CI: 0.543–0.941), heterozygous (AT vs. AA: p = 0.002; OR = 0.782, 95% CI: 0.667–0.917), dominant (TT+AT vs. AA: p = 0.002; OR = 0.768, 95% CI: 0.652–0.906), and recessive (TT vs. AA+AT: p = 0.042; OR = 0.802, 95% CI: 0.649–0.992) genetic models. In ethnicity-wise subgroup analysis, reduced risk of PTB was found in the Caucasian population. However, we did not find an association with any of the genetic models in the Asian population.ConclusionsIn conclusion, the IFN-γ +874 A>T gene polymorphism is significantly associated with reduced risk of PTB, showing a protective effect in the overall and in the Caucasian population. However, this polymorphism is not associated with PTB risk in the Asian population.     

Association of miR-27a polymorphism with the risk of digestive system cancers

BackgroundCancer of the digestive system is a common cancer and results in high mortality rates world-wide. miR-27a polymorphism has been associated with an increased risk of digestive system cancers; however, this has not been conclusively shown yet. Therefore, to clarify this, we conducted a comprehensive meta-analysis.MethodsPubMed, EMBASE, OVID and Cochrane Library databases were comprehensively searched to retrieve eligible studies published up to May 10, 2020 that referred to digestive cancers. Odds ratios and the corresponding 95 % confidence intervals (CI) were used when calculating the relationship between miR-27a rs895819 polymorphism and susceptibility to digestive cancers.ResultsA significant correlation between the miR-27a rs895819 polymorphism and the presence of digestive system cancers was found in four genetic models, which were the homozygote, dominant, recessive, and allele genetic models (GG vs AA: OR = 1.210, 95 %CI = 1.020–1.436, P = 0.029; GG + AG vs AA: OR = 1.092, 95 %CI = 1.024–1.164, P = 0.007; GG vs AG + AA: OR = 1.182, 95 %CI = 1.005–1.390, P = 0.044; G vs A: OR = 1.099, 95 %CI = 1.046–1.154, P < 0.001). Hierarchical analysis by ethnicity suggested that miR-27a rs895819 significantly increased the risk of digestive system cancers in the Asian population, but not in Caucasians. Additionally, rs895819 polymorphism was found to be significantly associated with colorectal cancer and gastric cancer.ConclusionsThe miR-27a rs895819 polymorphism may be associated with an increased risk for digestive system cancers.     

Hsa-mir-499 rs3746444 polymorphism and cancer risk: a meta-analysis

MicroRNAs(miRNAs) are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English(including 6134 cases and 7141 controls) were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients(G allele vs A allele:OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%) and population-based studies(G allele vs A allele:OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%).The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.     

Correlation between survivin genetic polymorphisms and lung cancer susceptibility

Aims: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. Results: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). Conclusions: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer.     

Association of CAV1 polymorphisms with the risks of breast cancer: A systematic review and meta-analysis

BackgroundCaveolin-1 (CAV1) polymorphisms have been shown to correlated with breast cancer risk in previous studies. However, the role of CAV1 polymorphisms still remained indecisive, and dual functions of CAV1 was demonstrated in breast cancer development. Consequently, a meta-analysis to evaluate and summarize the association of the CAV1 polymorphisms with breast cancer susceptibility.Material and methodsExtensive search was performed in PubMed, Web of Science, Google scholar, EMBASE.com, CNKI and Wanfang searching platform up to March 2019. The Newcastle–Ottawa Scale (NOS) were used to evaluate the quality of each study. The Odds ratios (ORs) and the 95% confidence intervals (CIs) were analyzed to evaluate the strength of the associations in five genetic models. Inter-study heterogeneity was quantified using the I-squared (I²) test. In addition, the Egger’s test and Begg’s test were applied to evaluate the publication bias.Results4 case-control studies with 2115 cases and 2138 controls were enrolled into this analysis. There was a significant association between rs3807987 polymorphism of CAV1 and breast cancer in allele comparison (A vs. G: OR = 1.288, 95％CI = 1.162–1.428, P < 0.001), heterozygote comparison (AG vs. GG: OR= 1.422, 95％CI=1.233–1.639, P < 0.001), and dominant comparison (AA+AG vs. GG: OR=1.395, 95％CI=1.228-1.586, P < 0.001). A significant association of rs3807987 polymorphism in allele comparison (A vs. G: OR=1.238, 95％CI=1.109–1.383, P < 0.001), heterozygote comparison (AG VS. GG: OR=1.466, 95％CI=1.267–1.697, P < 0.05), and dominant comparison (AA+AG vs. GG: OR=1.384, 95％CI=1.209–1.585, P < 0.001) was also founded amongst Chinese population. A significant association between rs7804372 polymorphism and breast cancer amongst Chinese population in recessive comparison (AA vs. AT + TT: OR = 0.730, 95％CI = 0.567–0.940, P = 0.015) was identified. No significant association between breast cancer risk and rs1997623 was found.ConclusionCAV1 rs3807987 and rs7804372 polymorphisms are associated with the change of breast cancer risk. More well-designed and large studies in various populations are needed to further elaborate these associations.     

Effect of TOP2A and ERCC1 gene polymorphisms on the efficacy and toxicity of cisplatin and etoposide-based chemotherapy in small cell lung cancer patients

IntroductionThe main treatment regimen for small cell lung cancer (SCLC) involves platinum-based chemotherapy (cisplatin or carboplatin) and etoposide. Single nucleotide polymorphisms (SNPs) in TOP2A and ERCC1 genes were tested as prognostic and predictive factors in non-small cell lung cancer (NSCLC). There are limited data about the clinical relevance of these genetic alterations in SCLC. We undertook this retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on the efficiency and toxicity of chemotherapy with platinum and etoposide in SCLC Caucasian patients.Material and methodsThe studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ±7.5 years). Detailed clinical-demographical data were collected and response to treatment was monitored. DNA was isolated from peripheral blood leukocytes using QIAamp DNA Mini Kit. Single nucleotide polymorphisms were analyzed using TaqMan hydrolyzing probes in real-time PCR technique on an Eco Illumina device.ResultsPatients with C/C genotype in rs13695 of the TOP2A gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients (p = 0.02, χ² = 5.51, OR = 2.676, 95% CI: 1.165–6.143). Patients harbouring homozygous C/C genotype in rs3212986 of the ERCC1 gene had significantly higher risk of anaemia during chemotherapy, than heterozygous C/A patients (p = 0.045, χ² = 4.01, OR = 0.417, 95% CI: 0.175–0.991). Furthermore, heterozygous G/A genotype in rs11615 of the ERCC1 gene was associated with significant shortening of OS (9 vs. 12 months) compared to homozygous A/A genotype (p = 0.01, χ² = 6.31, HR = 1.657, 95% CI: 1.0710–2.5633).ConclusionsSNPs in ERCC1 and TOP2 genes may be associated with the toxicities and survival of SCLC patients treated with cisplatin and etoposide.     

Association between EGFR polymorphisms and the risk of lung cancer

Target: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. Methods: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by χ² test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). Results: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). Conclusions: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer.     

Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population

MicroRNAs (miRNA) are thought to play important roles in the pathogenesis of diseases. Single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics via altering their target selection and/or expression, resulting in functional and/or phenotypic changes. We decided to investigate the genetic association with pulmonary tuberculosis with 2 nucleotide variations within corresponding microRNAs regulating the Toll-like receptor (TLR)-mediating signal pathway. MiRNAs potentially regulating the TLR-mediating signal pathway were predicted via bioinformatics. Finally, 2 SNPs, rs2910164 G>C and rs3746444 T>C within miR-146a and miR-499, were selected as candidates in accordance with some criteria. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and validated by sequencing to demonstrate their association with susceptibility to pulmonary tuberculosis (PTB) in 337 PTB cases and 738 healthy controls, including 318 Tibetan and 757 Han individuals. Bioinformatics databases were searched to support the association between miRNAs and PTB. There was no association between rs3746444 and PTB risk (p = 0.118) in the Han population, but subjects carrying the C allele exhibited decreased PTB risk (odds ratio [OR] = 0.403 [95% confidence interval (95% CI) 0.278-0.583]). However, there was an association between rs3746444 and PTB in the Tibetan population, and individuals carrying the C allele exhibited increased PTB risk (OR = 1.870 [95% CI 1.218-2.871]). A polymorphism (rs2910164 G>C) indicated an association with PTB risk in both Tibetan (p = 0.031) and Han (p = 0.000) populations. However, the role of the G allele of rs2910164, like the C allele in rs3746444, differed in the Tibetan (OR = 1.509, p < 0.05) and Han (OR = 0.575, p < 0.05) groups. This is the first report to suggest that a genetic association with pulmonary tuberculosis with SNPs within the corresponding miRNAs potentially regulates the TLR signal pathway. It is interesting that both the G allele (rs2910164) and the C allele (rs3746444) play different roles in 2 populations. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.     

Association of Polymorphism rs1045411 in the HMGB1 Gene with Cancer Risk: Evidence from a Meta-analysis

The high-mobility group box protein 1 (HMGB1) rs1045411 polymorphism has been demonstrated to be associated with cancer risk in some studies. However, the results regarding this topic are inconsistent. A meta-analysis was applied to elucidate the association between the HMGB1 rs1045411 polymorphism and cancer risk. Ten relevant studies were subjected to our analysis, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. In total, of 3,918 cases and 5,296 controls were included in this study. The pooled ORs were calculated using a random-effects or fixed-effects model according to the heterogeneity. The pooled results revealed that TT genotype was significantly related to increased cancer risk in the comparisons of TT vs. CC+TC (OR=1.35; 95% CI: 1.09-1.67; p=0.005). Though no statistical significance was achieved between HMGB1 rs1045411 polymorphism and cancer risk in other four genetic models (T vs. C: OR=1.08, 95% CI 0.90-1.30; TC vs. CC: OR=1.01, 95% CI 0.82-1.24; CC vs. TC+TT: OR=0.95, 95% CI 0.77-1.18; TT vs. CC: OR=1.42; 95% CI 0.98-2.05), a trend of increased risk could be drawn. In the subgroup analysis by type of malignancy and ethnicity, no obvious difference was found in the tumour risk regarding the HMGB1 rs1045411 polymorphism amongst the cancer types except for breast cancer (OR=1.94; 95% CI: 1.05-3.59; p=0.03) and hepatocellular carcinoma (OR=1.82; 95% CI: 1.15-2.88; p=0.01), while rs1045411 polymorphism was positively associated with risks of cancer amongst Hans (OR=1.37; 95% CI: 1.11-1.69; p=0.004) rather than Caucasians (OR=0.89; 95% CI: 0.26-3.02; p=0.01). These results suggest that the HMGB1 rs1045411 polymorphism might be associated with increased cancer risk.     

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Background/AimsNon-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD.MethodsWe evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed.ResultsCarriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis.ConclusionsThe KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.     

Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China

MicroRNAs (miRNAs) are a family of small noncoding RNAs that act as oncogenes and tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs may be associated with changes in phenotype and function. The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. A case-control study in 248 Kazakh patients with ESCC and 300 frequency matched control subjects was carried out to examine the potential association of six miRNA (miR-100 rs1834306, miR-34b/c rs4938723, miR-375 rs6715345, miR-146a rs2910164, miR-423 rs6505162 and miR-373 rs12983273) polymorphisms with risk of ESCC. We found that miR-100 rs1834306 T>C polymorphism was associated with a significant decreased risk of ESCC. In the recessive model, when the miR-100 rs1834306 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant decreased risk for ESCC (adjusted OR=0.495, 95% CI: 0.349-0.702, P=8.05×10^-5). In the dominant model, when the miR-100 rs1834306 TT genotypes was used as the reference group, the TC/CC genotype were associated with a borderline statistically decreased risk for ESCC (adjusted OR=0.665, 95% CI: 0.430-1.031, P=0.067). In addition, the miR-100 rs1834306 C allele in the Kazakh population was significantly associated with decreased risk of ESCC (OR=0.609, 95% CI: 0.48-0.78, P=8.37×10^-5). These findings indicated that functional polymorphism miR-100 rs1834306 C>T might contribute to decreased ESCC risk.     

Polymorphisms of the Homologous Recombination Gene RAD51 in Keratoconus and Fuchs Endothelial Corneal Dystrophy

Purpose. We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320) and c.-98G>C (rs 1801321) polymorphisms of the RAD51 gene and the occurrence of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) in dependence on some environmental factors. Methods. The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP. Results. The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75–5.13). On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31–0.88). We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28–0.92; crude OR 0.53, 95% CI 0.30–0.92, resp.), while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01–3.36; crude OR 1.90, 95% CI 1.09–3.29, resp.). Conclusions. The c.-61T/T and c.-98G>C polymorphisms of the RAD51 gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.     

TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean Population

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.

Graphical Abstract

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