Dataset Information

Association between HIF-1? gene polymorphisms and lung cancer: A meta-analysis.

ABSTRACT: Hypoxia-inducible factor-1 (HIF-1), an important component of angiogenesis, is activated as a response to tumor hypoxia and facilitates tumor survival. Several case-control articles stressed the connection between lung cancer danger and HIF-1? gene polymorphism, but the conclusions were conflicting. Thus, this meta-analysis was carried out to assess the connection between HIF-1? gene polymorphisms (rs11549467, rs11549465, and rs2057482) and lung cancer risk.PubMed, Embase, Cochrane Library, and Google Scholar were systematically searched up to November 1, 2018. The study quality was quantified by the c. The odds ratios (ORs) and 95% confidence intervals (CIs) were pooled in 5 genetic models for assessment under a fixed- or random-effect model. Subgroup analyses were carried out by ethnicity and genotype method. Sensitivity analysis and publication bias were tested. Five eligible articles were enrolled.The rs11549467 significantly increased the lung cancer risk (OR [95% CI]: A vs G, 1.68 [1.03-2.76]; AA + AG vs GG, 1.70 [1.14-2.54]; AA vs GG, 1.59 [1.21-2.10]), whereas neither rs11549465 nor rs2057482 was related with the lung cancer risk. Subgroup analysis showed rs11549465 and rs11549467 increased lung cancer risk among Asians, but not whites. HIF-1? rs2057482 was unrelated to the risk of lung cancer in Asians and whites.HIF-1? gene rs11549465 and rs11549467, but not rs2057482, increased the risk of lung cancer among Asians.

SUBMITTER: Xu S

PROVIDER: S-EPMC7302596 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Association between HIF-1α gene polymorphisms and lung cancer: A meta-analysis.

Xu Shuguang S Ying Kejing K

Medicine 20200601 24

Hypoxia-inducible factor-1 (HIF-1), an important component of angiogenesis, is activated as a response to tumor hypoxia and facilitates tumor survival. Several case-control articles stressed the connection between lung cancer danger and HIF-1α gene polymorphism, but the conclusions were conflicting. Thus, this meta-analysis was carried out to assess the connection between HIF-1α gene polymorphisms (rs11549467, rs11549465, and rs2057482) and lung cancer risk.PubMed, Embase, Cochrane Library, and ...[more]

PMID: 32541494

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Project description:Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymorphisms are thought to influence the risk of cancer and radiation-induced pneumonitis (RP) risk in cancer patients treated with radiotherapy. However, the results of previous studies are inconsistent. We therefore conducted this comprehensive meta-analysis.A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015). The odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of these relationships. Funnel plots and Begg's and Egger's tests were conducted to assess the publication bias. All analyses were performed in STATA 13.0 software.Ten eligible case-control studies (4731 cases and 5142 controls) on lung cancer susceptibility and four (192 cases and 772 controls) on RP risk were included. The results of the overall and subgroup analyses indicated that in the ATM gene, the rs189037 (-111G?>?A, -4519G?>?A), rs664677 (44831C?>?T, 49238C?>?T) and rs664143 (131,717 T?>?G) polymorphisms were significantly associated with lung cancer susceptibility (OR?=?1.21, 95% CI?=?1.04-1.39, P?=?0.01; OR?=?1.26, 95% CI?=?1.06-1.49, P?=?0.01; OR?=?1.43, 95% CI?=?1.15-1.78, P?<?0.01). Additionally, the rs189037 variant was significantly associated with RP risk (OR?=?1.74, 95% CI?=?1.02-2.97, P?=?0.04). No publication bias was found in the funnel plots, Begg's tests or Egger's tests.The results indicate that the ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer, while the ATM rs189037 variant was significantly associated with RP risk.

Project description:BACKGROUND: X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of XRCC1 are suspected to have some relationship with response to chemotherapy and overall survival of lung cancer. This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients. METHODS: We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected using specific inclusion and exclusion criteria. Primary outcomes included objective response (i.e., complete response + partial response vs. progressive disease + stable disease) and overall survival (OS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software. RESULTS: Twenty-two articles were included in the present analysis. XRCC1 Arg194Trp and Arg399Gln polymorphisms were significantly associated with response to treatment in lung cancer patients. Patients with C/T genotype, T/T genotype and minor variant T allele at Arg194Trp were more likely to respond to platinum-based chemotherapy compared with those with C/C genotype (C/T vs. C/C: OR, 2.54; 95%CI, 1.95-3.31; T/T vs. C/C: OR, 2.06; 95%CI, 1.39-3.06; C/T+T/T vs. C/C: OR, 2.42; 95% CI, 1.88-3.10). For XRCC1 Arg399Gln, G/A genotype, A/A genotype and minor variant A allele were associated with objective response in all patients (G/A vs. G/G: OR, 0.67; 95%CI, 0.50-0.90; A/A vs. G/G: OR, 0.43; 95%CI, 0.25-0.73; A/A+G/A vs. G/G: OR, 0.63; 95%CI, 0.49-0.83). Both G/A and A/A genotypes of XRCC1 Arg399Gln could influence overall survival of lung cancer patients (G/A vs. G/G: HR, 1.23; 95%CI, 1.06-1.44; A/A vs. G/G: HR, 2.03; 95%CI, 1.20-3.45). Interaction analysis suggested that compared with the patients carrying C/T+T/T genotype at XRCC1 194 and G/G genotype at XRCC1 399, the patients carrying 194 C/C and 399 G/A+A/A or 194 C/C and 399 G/G genotype showed much worse objective response. CONCLUSIONS: Genetic polymorphisms in XRCC1 gene might be associated with overall survival and response to platinum-based chemotherapy in lung cancer patients.

Project description:BackgroundThe association between polymorphisms on 15q25.1 and lung cancer has been widely evaluated; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two polymorphisms (CHRNA3 gene: rs1051730 and AGPHD1 gene: rs8034191) on 15q25.1.MethodsData were extracted from 15 and 14 studies on polymorphisms rs1051730 and rs8034191 involving 12301/14000 and 14075/12873 lung cancer cases/controls, respectively. The random-effects model was applied, addressing heterogeneity and publication bias.ResultsThe two polymorphisms followed Hardy-Weinberg equilibrium for all studies (P>0.05). For rs1051730-G/A, carriers of A allele had a 36% increased risk for lung cancer (95% confidence interval [CI]: 1.27-1.46; P<0.0005), without heterogeneity (P = 0.258) or publication bias (P(Egger) = 0.462). For rs8034191-T/C, the allelic contrast indicated that C allele conferred a 23% increased risk for lung cancer (95% CI: 1.08-1.4; P = 0.002), with significant heterogeneity (P<0.0005), without publication bias (P(Egger) = 0.682). Subgroup analyses suggested that the between-study heterogeneity was derived from ethnicity, study design, matched information, and lung cancer subtypes. For example, the association of polymorphisms rs1051730 and rs8034191 with lung cancer was heterogeneous between Caucasians (OR = 1.32 and 1.22; 95% CI: 1.25-1.44 and 1.05-1.42; P<0.0005 and 0.008, respectively) and East Asians (OR = 1.51 and 1.03; 95% CI: 0.76-3 and 0.47-2.27; P = 0.237 and 0.934, respectively) under the allelic model, and this association was relatively strengthened under the dominant model. There was no observable publication bias for both polymorphisms.ConclusionsOur findings demonstrated that CHRNA3 gene rs1051730-A allele and AGPHD1 gene rs8034191-T allele might be risk-conferring factors for the development of lung cancer in Caucasians, but not in East-Asians.

Dataset Information

Association between HIF-1? gene polymorphisms and lung cancer: A meta-analysis.

Publications

Association between HIF-1α gene polymorphisms and lung cancer: A meta-analysis.

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