A meta-analysis of MDR1 polymorphisms rs1128503 and rs1045642 and susceptibility to hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Chang Q
PROVIDER: S-EPMC6683882 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
A meta-analysis of <i>MDR1</i> polymorphisms rs1128503 and rs1045642 and susceptibility to hepatocellular carcinoma.
Chang Qing Q He Zhong-Lin ZL Peng Yu-Chong YC Duan Shi-Gang SG Dai Yu-Xin YX Zhao Xiao-Hui XH
The Journal of international medical research 20190624 7
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Project description:ObjectiveGenetic polymorphisms can influence the chemotherapeutic response; however, previous studies have produced conflicting results, and have failed to identify the most relevant polymorphisms for predicting the response to treatment in patients with cancer. The present meta-analysis was conducted to determine the correlation between two polymorphisms (rs1045642 and rs1128503) in ATP-binding cassette transporter B subfamily member 1 (ABCB1), which is associated with multidrug resistance, and the survival of patients treated with taxane-containing chemotherapy.MethodsSeveral databases, including PubMed and Embase, were used to retrieve articles evaluating the association between the ABCB1 rs1045642 and rs1128503 polymorphisms and survival, published prior to August 2019. The meta-analysis was conducted using R software to determine the pooled hazard ratio (HR) and 95% confidence intervals (95% CIs).ResultsFifteen studies involving 3320 patients were included in the meta-analysis. The effect of the rs1128503 polymorphism on progression-free survival remained significant in the heterozygote (HR 0.81; 95% CI: 0.67-0.98) and homozygote (HR 0.71; 95% CI: 0.58-0.88) models. The TT genotype rs1128503 was associated with better overall survival (HR 0.72; 95% CI: 0.53-0.97).ConclusionCarriers of the rs1128503 T allele of ABCB1 showed a survival benefit after taxane-containing chemotherapy.
| S-EPMC8184199 | biostudies-literature
Project description:AimTo assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility.MethodsTwo investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.ResultsThis meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identified as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32).ConclusionThis meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC.
| S-EPMC3198024 | biostudies-literature
Project description:Multidrug resistance 1 (MDR1) is a transmembrane transporter on the cell membrane. As an ATP-dependent efflux pump, MDR1 is mainly responsible for the adsorption, distribution, metabolism, excretion and transportation of anticancer drugs to cancer cells. Mutations of the MDR1 gene may be associated with the incidence of cancer. In the past decade, associations found between the MDR1 rs1045642 polymorphism and breast cancer have been inconsistent and inconclusive. Therefore, the present study performed a meta-analysis including studies published up until August 16, 2023 to systematically evaluate the association between the MDR1 rs1045642 polymorphism and breast cancer risk. A total of 21 published case studies involving 6,815 patients with breast cancer and 9,227 healthy participants were included in the meta-analysis. Overall, the MDR1 rs1045642 polymorphism was not significantly associated with breast cancer-associated risk. However, in the subgroup analysis, the MDR1 rs1045642 polymorphism was found to be notably associated with a higher risk of breast cancer among Asian populations in recessive models [TT vs. CT + CC; odds ratio (OR)=1.393; 95% confidence interval (CI), 1.143-1.698; P=0.001; I2<25%]. The MDR1 C3435T polymorphism was also associated with a notable decrease in the incidence of breast cancer in mixed ethnicity populations (TT and CT + CC; OR=0.578; 95% CI, 0.390-0.856; P=0.006; I2<25%). In Caucasian populations, the MDR1 rs1045642 polymorphism was not associated with breast cancer risk. In conclusion, the present meta-analysis demonstrated that the MDR1 rs1045642 polymorphism may increase the risk of breast cancer in Asian populations, is associated with a reduced risk of breast cancer in mixed populations but has no notable effect in Caucasian populations.
| S-EPMC10921258 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV).MethodsDatabases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines.ResultsA total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs.ConclusionMiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.
| S-EPMC7851082 | biostudies-literature
Project description:BACKGROUND: Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship. METHODS: Meta-analysis was performed on the associations between the miR-146a rs2910164 C?>?G and miR-499 rs3746444 T?>?C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study. RESULTS: Results show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR?=?1.153, 95% CI 1.083-1.228, P?<?0.001; GC versus CC: OR?=?1.165, 95% CI 1.054-1.286, P?=?0.003; GG versus CC: OR?=?1.361, 95% CI 1.192-1.553, P?<?0.001; GG/GC versus CC: OR?=?1.213, 95% CI 1.104-1.333, P?<?0.001; GG versus GC/CC: OR?=?1.210, 95% CI 1.080-1.356, P?<?0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR?=?2.171, 95% CI?=?1.149-4.104, P?=?0.017) than those with TT genotype. CONCLUSIONS: We conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.
| S-EPMC4236519 | biostudies-literature
Project description:BackgroundAssociations between polymorphisms in vitamin D receptor (VDR)/vascular endothelial growth factor (VEGF)/interleukin-18 (IL-18)/mannose-binding lectin (MBL) and susceptibility to hepatocellular carcinoma (HCC) were already explored by many studies, yet the results of these studies were inconsistent. The aim of this meta-analysis was to better clarify associations between polymorphisms in VDR/VEGF/IL-18/MBL and HCC by combing the results of all relevant studies.MethodsEligible publications were searched from PubMed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies.ResultsThirty studies were included in this study. Combined results revealed that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms were all significantly associated with HCC in the overall pooled population. We also obtained similar significant associations for VDR rs7975232, VDR rs2228570, IL-18 rs1946518, and MBL rs7096206 polymorphisms in Asians.ConclusionsCollectively, this meta-analysis proved that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to HCC in certain populations.
| S-EPMC6909495 | biostudies-literature
Project description:BackgroundStudies have investigated rs1128503, rs1045642, and rs2032582 in multidrug resistance protein 1 (MDR1) for association with susceptibility to idiopathic nephrotic syndrome (INS) and steroid resistance. However, because these findings were inconsistent, we performed a meta-analysis to determine whether there was evidence of a role of these MDR1 variants in INS.MethodsThe PubMed, Embase, and Web of Science databases were systematically searched to identify studies that examined MDR1 polymorphisms with susceptibility to INS and/or to steroid resistance. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model based on heterogeneity.ResultsWe selected 9 case-control studies that included 928 patients with INS, of which steroid resistance data were available for 724 (236 were steroid resistant and 488 were steroid sensitive), and 879 healthy controls. All subjects were children. No significant relationships between these polymorphisms and INS susceptibility were identified. Significantly increased risk of steroid resistance was observed with rs1128503 allelic (OR = 1.49, 95% CI = 1.20-1.86) and genotypic (OR = 1.97, 95% CI = 1.18-3.30; OR = 2.03, 95% CI = 1.43-2.88) comparisons, and with allelic (OR = 1.56, 95% CI = 1.05-2.31) and genotypic (OR = 2.85, 95% CI = 1.15-7.07; OR = 2.21, 95% CI = 1.01-4.8) comparisons to rs2032582 in Caucasian populations. However, this association between rs2032582 and steroid resistance was not robust enough to withstand corrections for multiple comparisons. Similarly, we found that the rs1128503T-rs2032582G-rs1045642C (T-G-C) haplotype was associated with an increased risk of steroid resistance (OR = 2.02, 95% CI = 1.13-3.59), while the wild-type C-G-C haplotype was associated with a decreased risk (OR = 0.32, 95% CI = 0.12-0.88) in Caucasians; however, these findings were not significant following adjustments for multiple comparisons.ConclusionsMDR1 rs1128503, rs1045642, and rs2032582 polymorphisms are not associated with INS susceptibility; however, there is evidence of an association between rs1128503 and increased risk of steroid resistance in children with INS, which indicates MDR1 may play a role in steroid resistance found in children with INS.
| S-EPMC5478346 | biostudies-literature
Project description:BACKGROUND: Single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the process of carcinogenesis by altering the expression of tumor-related microRNAs. It has been suggested that two common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association between the two SNPs and the risk for HCC. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a search of case-control studies on the associations of SNPs rs2910164 and/or rs11614913 with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, ScienceDirect, Wiley Online Library and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with the two polymorphisms was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). 5 studies on rs2910164 and 4 studies on rs11614913 were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distribution of the two polymorphisms was associated with risk for HCC in all genetic models. Similarly, subgroup analysis in Chinese population showed no association between the two SNPs and the susceptibility to HCC. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that two common SNPs rs2910164 and rs11614913 are not associated with the risk of HCC. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.
| S-EPMC3386926 | biostudies-literature
Project description:Aim of the studyWe reported the association between interleukin 6 polymorphisms (rs1800796, rs1800795, rs2069837, rs17147230, and rs1800797) and hepatocellular carcinoma (HCC) susceptibility in a meta-analysis.Material and methodsThe studies were retrieved by searching the search terms in Scopus, PubMed, Web of Science, and Cochrane Library databases until June 2020. The analyses were done by RevMan 5.3 software using odds ratios (ORs) and 95% confidence intervals (CIs) and the analysis of publication bias and sensitivity analyses were performed by CMA 2.0 software.ResultsSearching through the databases, 316 records were retrieved and finally 13 studies were analyzed in the present meta-analysis. For the rs1800797 polymorphism, there was an elevated risk of AA genotype (OR = 2.68, p = 0.03) in HCC patients compared to healthy controls. Also, there was an elevated risk of AA (OR = 3.06, p = 0.04) and GA (OR = 2.61, p = 0.005) genotypes in HCC patients compared to liver cirrhosis patients. For rs2069837 polymorphism, there was an elevated risk of GG genotype (OR = 2.25, p = 0.01) in HCC patients compared to healthy controls. For rs17147230, T allele (OR = 1.31, p = 0.03) and TT genotype (OR = 1.83, p = 0.02) had elevated risks in HCC patients compared to healthy controls.ConclusionsThe present meta-analysis confirmed that there was an elevated risk of the AA and GA genotypes of rs1800797 polymorphism and the GG genotype of rs2069837, and the T allele and TT genotype of rs17147230 in HCC.
| S-EPMC7816640 | biostudies-literature
Project description:PurposeOur study was carried out to explore the relationship of PIK3CA rs17849071 and rs17849079 polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese Han population.Methods150 HCC patients and 152 healthy individuals were recruited in the case and control groups respectively. The genotypes of PIK3CA rs17849071 and rs17849079 polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The linkage disequilibrium and haplotypes were analyzed with Haploview software. Differences in frequencies of genotypes, alleles, and haplotypes between the case and control groups were checked with χ(2) test. The controls were matched with the cases in age and gender. The relative risk of HCC was represented by odds ratio (OR) and 95% confidence interval (95% CI).ResultsSignificant difference in frequencies of GG genotype and G allele in PIK3CA rs17849071 polymorphism existed between the two groups (P=0.040; P=0.028), indicating that rs17849071 was closely related to the increased risk of HCC (OR=2.919, 95% CI=1.007-8.460; OR=1.642, 95% CI=1.051-2.564). Furthermore, TT genotype also significantly increased the susceptibility to HCC (OR=3.438, 95% CI=1.050-11.250) and so was T allele (OR=1.521, 95% CI=1.052-2.199). The haplotype analysisshowed that G-T haplotypes were higher in cases than that of controls (P=0.030), which suggested that G-T might be a susceptible haplotype to HCC.ConclusionsThe PIK3CA rs17849071 and rs17849079 polymorphisms may increase the risk of HCC either independently or synergistically.
| S-EPMC4713662 | biostudies-literature