Dataset Information

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

ABSTRACT:

Background

Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.

Objectives

An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A).

Methods

Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations.

Results

Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR?=?1.24, 95% CI: 1.04-1.48, P?=?0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR?=?0.78, 95% CI: 0.67-0.90, P?=?0.001; dominant: CG/CC vs.GG, OR?=?0.79, 95% CI: 0.69-0.91, P?=?0.001).

Conclusion

Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.

SUBMITTER: Zhu J

PROVIDER: S-EPMC4026486 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

Zhu Jinhong J Hua Rui-Xi RX Jiang Jing J Zhao Li-Qin LQ Sun Xiuwei X Luan Jinwei J Lang Yaoguo Y Sun Yanqi Y Shang Kun K Peng Shiyun S Ma Jianqun J

PloS one 20140519 5

<h4>Background</h4>Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.<h4>Objectives</h4>An updated meta-analysis was conducted to ...[more]

PMID: 24841208

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Project description:BACKGROUND: HIF-1 (hypoxia-inducible factor 1) is a transcriptional activator that functions as a critical regulator of oxygen homeostasis. Recently, a large number of epidemiological studies have investigated the relationship between HIF-1? C1772T/G1790A polymorphisms and cancer susceptibility. However, the results remain inconclusive. Therefore, we performed a meta-analysis on all of the available case-control studies to systematically summarize the possible association. METHODS: A literature search was performed using PubMed and the Web of Science database to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between HIF-1? C1772T/G1790A polymorphisms and cancer susceptibility were calculated using fixed- and random-effects models when appropriate. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis. RESULTS: A total of 40 studies met the inclusion criteria were included in the meta-analysis: 40 studies comprised of 10869 cases and 14289 controls for the HIF-1? C1772T polymorphism and 30 studies comprised of 7117 cases and 10442 controls for the HIF-1? G1790A polymorphism. The results demonstrated that there were significant association between the HIF-1? C1772T polymorphism and cancer susceptibility under four genetic models (TT vs. CC: OR = 1.63, 95% CI = 1.02-2.60; CT + TT vs. CC: OR = 1.15, 95% CI = 1.01-1.34; TT vs. CT + CC: OR = 2.11, 95% CI = 1.32-3.77; T vs. C: OR = 1.21, 95% CI = 1.04-1.41). Similarly, the statistically significant association between the HIF-1? G1790A polymorphism and cancer susceptibility was found to be consistently strong in all of the genetic models. Moreover, increased cancer risk was observed when the data were stratified by cancer type, ethnicity and the source of controls. CONCLUSIONS: This meta-analysis demonstrates that both the C1772T and G1790A polymorphisms in the HIF-1? gene likely contribute to increased cancer susceptibility, especially in the Asian population and in breast cancer, lung cancer, pancreatic cancer and oral cancer. However, further research is necessary to evaluate the relationship between these polymorphisms and cancer risk.

Project description:BackgroundAs one of the most common body malignant cancers, skin cancers contain a group of highly heterogeneous tumors with different malignant potential, prognosis and treatment methods. Despite the progress in the treatment of skin cancers worldwide, the overall prognosis is still poor. Recent studies indicated single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6), including 174G/C and 597G/A, might be associated with susceptibility to skin cancer. This meta-analysis aims to clarify the relationship between IL-6 gene polymorphisms and skin cancers.MethodsEligible studies were identified from searching PubMed, Embase, Web of Science and Cochrane. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were obtained for the relationships between IL-6 174G/C and 597G/A polymorphisms and skin cancer using random-effects models. For the included studies, the Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. Trim-and-fill method was used when publication bias existed aiming to adjusting OR. All data were analyzed in R (version 4.0.2).ResultsThis meta-analysis included 1,705 cases and 1,987 controls for 174G/C polymorphism (10 publications), and 968 cases and 998 controls for 597G/A polymorphism (3 publications). No elevated risk of skin cancer was found in all comparisons for 174G/C polymorphism: CC vs. GC + GG, OR =1.03 (95% CI: 0.81-1.31); GC + CC vs. GG, OR =1.16 (95% CI: 0.96-1.39); CC vs. GG, OR =1.14 (95% CI: 0.86-1.53); GC vs. GG, OR =1.16 (95% CI: 0.99-1.37); C vs. G, OR =1.07 (95% CI: 0.92-1.24). Then we performed subgroup analysis based on publication year, the cancer type, sample size, NOS score. Significant differences were observed in the subgroup of publication year before 2010 (GC + CC vs. GG, OR =1.255, P=0.012; GC vs. GG, OR =1.277, P=0.01), while there is no statistical significance in the subgroup of publication year after 2010 (P>0.05 for all comparisons). After publication bias adjustment, the results further suggested that 174G/C polymorphism is not associated with the risk of skin cancer. No elevated risk of skin cancer was found in the comparisons for 597G/A polymorphism.DiscussionCurrent evidence showed that IL-6 gene polymorphisms might not be associated with the susceptibility to skin cancer.

Dataset Information

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

Background

Objectives

Methods

Results

Conclusion

Publications

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

Similar Datasets

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