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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 571-574

Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer


Department of Respiratory Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

Date of Web Publication9-Oct-2015

Correspondence Address:
Qingyu Xiu
415 Fengyang Road, Shanghai 200003
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.159085

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 > Abstract 

Aims: X-ray repair cross complementing group 1 (XRCC1) has been indicated to be correlated with the efficacy of platinum-based chemotherapy. But study results were still debatable. Thus, a meta-analysis was conducted.
Materials and Methods: A literature search was performed using the PubMed, EMBASE, CNKI, with the databases being last accessed on November 24, 2014. Odds ratios with 95% confidence intervals were used to assess the strength of the association.
Results: In this meta-analysis, we found that XRCC1 Arg194Trp polymorphism was significantly associated with the efficacy of platinum-based chemotherapy. However, XRCC1 Arg399Gln polymorphism showed no impact on the efficacy of platinum-based chemotherapy.
Conclusion: This meta-analysis suggested that the XRCC1 Arg194Trp polymorphism may be associated with efficacy of platinum-based chemotherapy. Further studies with a larger sample size are needed to further assess this result.

Keywords: Meta-analysis, nonsmall cell lung cancer, platinum, X-ray repair cross complementing group 1


How to cite this article:
Fan X, Xiu Q. Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer. J Can Res Ther 2015;11:571-4

How to cite this URL:
Fan X, Xiu Q. Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer. J Can Res Ther [serial online] 2015 [cited 2019 Nov 21];11:571-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/571/159085


 > Introduction Top


Lung cancer is one of the most dangerous diseases. [1] Although improvements in the treatment of lung cancer, [2] the prognosis remained poor. The 5-year survival of nonsmall cell lung cancer (NSCLC) ranged of 5-10%. [3] The most used first-line regimen for NSCLC was platinum-based doublet chemotherapy. [4] However, some NSCLC patients achieved remission, others achieved stable, and the remaining NSCLC patients achieved progressive disease. [5],[6]

X-ray repair cross complementing group 1 (XRCC1) was a critical component of DNA repair. XRCC1 encoded a scaffolding protein, which participated in the base excision repair pathway. [7],[8] Some nonsynonymous coding polymorphisms such as Arg399Gln and Arg194Trp, were identified. [9] Recent studies revealed that certain genetic polymorphisms including XRCC1 are associated with the treatment response of platinum-based chemotherapy in advanced NSCLC. [10] Many studies investigated the association between XRCC1 polymorphisms and the efficacy of platinum-based chemotherapy. [11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37] However, the results were still uncertain. Thus, we did a meta-analysis to determine whether XRCC1 polymorphisms influenced the efficacy of platinum-based chemotherapy.


 > Materials and methods Top


Publication search

A literature search was performed using the PubMed, EMBASE, CNKI, with the databases being last accessed on November 24, 2014. References from relevant articles were manually checked for further studies. Combination of the following terms was applied: "NSCLC" or; "platinum" or; "XRCC1."

Inclusion and exclusion criteria

The major inclusion criteria were: (1) Cohort studies; (2) investigating the association between XRCC1 polymorphisms and the efficacy of platinum-based chemotherapy; (3) available genotype distribution information or odds ratio (OR) with its 95% confidence intervals (CIs). The major reasons for exclusion of studies were: (1) Reviews and repeated literature; (2) animal studies; (3) overlapped studies.

Data extraction and quality assessment

The following data were recorded from each article: First author, year of publication, race of participants, gender, numbers of patients, and studied polymorphisms. The data were extracted by two of the authors independently. Discrepancies between these two authors were resolved by discussion. Newcastle-Ottawa Scale was used to evaluate the quality of the each study.

Statistical analysis

The strength of association between XRCC1 polymorphisms and the efficacy of platinum-based chemotherapy were assessed by calculating OR with 95% CI. A statistical test for heterogeneity was performed based on the Q statistic. The P > 0.10 of the Q-test indicated a lack of heterogeneity among studies. If heterogeneity was observed among the studies, the random-effects model was used to estimate the pooled OR (the DerSimonian and Laird method). Otherwise, the fixed-effects model was adopted (the Mantel-Haenszel method). Sensitivity analysis was conducted through sequentially excluded individual studies to assess the stability of the results. Potential publication bias was examined by Egger's test. All statistical tests were performed with the software STATA version 11.0 (Stata Corporation, College station, TX, USA). A P > 0.05 was considered statistically significant. Bonferroni correction was applied.


 > Results Top


Characteristics of studies

A total of 29 studies with 4711 NSCLC patients on the association between XRCC1 polymorphisms and the efficacy of platinum-based chemotherapy were included for this meta-analysis [Figure 1]. There were 14 studies of Asian population and 15 studies of Caucasian population. The characteristics of each study are presented in [Table 1]. All the included studies were high quality.
Figure 1: Flow diagram for study selection in meta-analysis

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Table 1: The characteristics of the studies

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Results of meta-analysis

As shown in [Table 2], NSCLC patients with XRCC1 399AA genotype did not show significantly increased efficacy of platinum-based chemotherapy when compared to the patients with XRCC1 399GG genotype (OR = 1.11; 95% CI 0.68-1.82; P = 0.70). Furthermore, when compared to the patients with XRCC1 399AG genotype, this polymorphism also did not influence the efficacy of platinum-based chemotherapy (OR = 1.29; 95% CI 0.76-2.03; P = 0.67). In addition, NSCLC patients with XRCC1 399AA genotype also did not show significantly increased efficacy of platinum-based chemotherapy when compared to the patients with XRCC1 399GG or 399AG genotype (OR = 1.22; 95% CI 0.65-2.27; P = 0.57). A single study involved in the meta-analysis was deleted each time to reflect the influence of the individual data set to the pooled ORs, and the corresponding pooled ORs were not materially altered (data not shown). Egger's test was performed to assess the publication bias of literature. Egger's test did not find the evidence of publication bias [Table 2].
Table 2: The results of this meta-analysis

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As for XRCC1 Arg194Trp polymorphism, patients with TT or CT genotype showed increased efficacy of platinum-based chemotherapy (OR = 1.65; 95% CI 1.29-2.10; P < 0.01 and OR = 1.63; 95% CI 1.35-1.96; P < 0.01). In addition, NSCLC patients with XRCC1 194TT or 194CT genotype showed significantly increased efficacy of platinum-based chemotherapy when compared to the patients with XRCC1 194CC genotype (OR = 1.64; 95% CI 1.39-1.93; P < 0.01). We conducted one-way sensitivity analysis to evaluate the stability of the meta-analysis. The statistical significance of the results was not altered when any single study was omitted (data not shown). Egger's test did not indicate significant publication bias [Table 2].


 > Discussion Top


Previous studies showed that XRCC1 Arg399Gln and Arg194Trp polymorphisms could increase the risk of NSCLC. [38],[39] However, the role of XRCC1 Arg399Gln and Arg194Trp polymorphisms on the efficacy of platinum-based chemotherapy was still inconsistent. Therefore, we performed this study to assess the association between XRCC1 Arg399Gln and Arg194Trp polymorphisms and efficacy of platinum-based chemotherapy. In this meta-analysis, we found that XRCC1 Arg194Trp polymorphism was significantly associated with the efficacy of platinum-based chemotherapy. However, XRCC1 Arg399Gln polymorphism showed no impact on the efficacy of platinum-based chemotherapy.

Platinum agents were activated intracellularly. Platinum could bind to DNA and induce DNA adducts, which could lead to cell death. It is possible that if cancer cells could enhance the ability to repair DNA damage made by platinum, this may lead to the resistant to chemotherapy. Previous study suggested that patients with platinum-based chemotherapy and a lower DNA repair capacity could increase survival rate. [40] XRCC1 Arg194Trp polymorphism decreased the ability to repair DNA damage. Thus, this polymorphism was associated with increased efficacy of platinum-based chemotherapy.

The present meta-analysis had several limitations. First, due to lacking of the original data of the eligible studies, we could not perform subgroup analyses based on age, smoking, and so on. Second, the numbers of published studies were not sufficient for a comprehensive analysis, particularly for Africans. However, our meta-analysis also had some merits. First, we investigated the association between two polymorphisms and efficacy of platinum-based chemotherapy. Second, there was no publication bias in this meta-analysis.

This meta-analysis suggested that the XRCC1 Arg194Trp polymorphism may be associated with efficacy of platinum-based chemotherapy. Further studies with a larger sample size are needed to further assess this result.

 
 > References Top

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