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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1084-1090

An updated meta-analysis for association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer


Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

Date of Web Publication11-Dec-2018

Correspondence Address:
Hua-Fu Zhou
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.199455

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 > Abstract 


Aim of Study: The conclusions on the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and lung cancer risk are still debated. This meta-analysis was performed to update the association between GSTP1 and the risk of lung cancer.
Materials and Methods: The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method.
Results: Fifty reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility. The association between GSTPI G allele/GG genotype and lung cancer risk was found in this meta-analysis (G allele: odds ratio [OR] = 1.08, 95% confidence interval [CI]: 1.02–1.14, P = 0.006; GG genotype: OR = 1.09, 95% CI: 1.00–1.18, P = 0.04). However, the AA genotype was not associated with the susceptibility of lung cancer.
Conclusion: GSTP1 G allele/GG genotype is associated with the lung cancer susceptibility.

Keywords: A/G gene polymorphism, glutathione S-transferase P1, lung cancer, updated meta-analysis


How to cite this article:
Liu WZ, Sun Y, Feng X, Bi XH, Liu T, Zhou HF. An updated meta-analysis for association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer. J Can Res Ther 2018;14, Suppl S5:1084-90

How to cite this URL:
Liu WZ, Sun Y, Feng X, Bi XH, Liu T, Zhou HF. An updated meta-analysis for association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer. J Can Res Ther [serial online] 2018 [cited 2019 Sep 17];14:1084-90. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1084/199455




 > Introduction Top


Lung cancer is the leading cause of cancer-related death worldwide. For early stages of the disease, lung resection surgery remains the best treatment with curative intent, but significant morbidity is associated, especially among patients with poor pulmonary function and cardiorespiratory fitness.[1] The dismal lethality of lung cancer is due to late stage at diagnosis, and the early diagnosis and incorporation of targeted therapies have modestly improved clinical outcomes.[2] Developing an indicator for the early diagnosis of lung cancer is urgently needed.

The current evidence indicate that glutathione S-transferases (GSTs) can take part in the pathogenesis of cancers. The human GSTP1 A/G gene polymorphism is polymorphic with an A to G transition in exon 5 causing a replacement 105 Ile to Val in the GSTP1 protein. In our previous meta-analysis,[3] we found that GSTP1 G allele was associated with the lung cancer susceptibility. This meta-analysis was performed to update the results in our previous meta-analysis, by including more studies.


 > Materials and Methods Top


Search strategy for the relationship between glutathione S-transferase P1 gene polymorphism and the risk of lung cancer

The relevant studies were searched from the electronic databases of PubMed and Cochrane Library on May 1, 2016. The retrieval strategy of “(glutathione S-transferase P1 OR GSTP1) AND (polymorphism OR polymorphisms OR genotype OR genotypes OR allele OR alleles) AND (lung cancer OR lung carcinoma OR pulmonary carcinoma)” was entered into these databases. The additional reports were identified through references cited in recruited articles.

Inclusion and exclusion criteria

Inclusion criteria

  • The outcome had to be lung cancer
  • There had to be at least two comparison groups (lung cancer group vs control group)
  • The investigation should provide the data of GSTP1 A/G genotype distribution.


Exclusion criteria

  • Review articles and editorials
  • Case reports
  • Preliminary result not on GSTP1 gene polymorphism or outcome
  • Investigating the role GSTP1 gene expression to disease
  • If multiple publications for the same data from the same study group occurred, we only recruited the later paper into our final analysis.


Data extraction

The following information from each eligible study was extracted independently by two investigators:First author's surname, year of publication, ethnicity, control source of the control group and the number of cases and controls for GSTP1 genotypes. Frequencies of G allele of GSTP1 were calculated for case group and control group, from the corresponding genotype distribution. The results were compared, and disagreement was resolved by discussion.

Statistical analysis

Cochrane Review Manager Version 5 (Cochrane Library, UK) was used to calculate the available data from each investigation. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the P value of heterogeneity test was <0.1. Results were expressed with odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. P < 0.05 was required for the pooled OR to be statistically significant. I2 was used to test the heterogeneity among the included studies. Sensitivity analysis was also performed according to the source of the controls (population vs. hospital).


 > Results Top


Study characteristics

Fifty studies[4],[5],[6],[7],[8],[9],[10],[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],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53] reporting the relationship between GSTP1 A/G gene polymorphism and lung cancer susceptibility were recruited into this meta-analysis. The data of our interest were extracted, and the frequencies of G allele of GSTP1 for case group and control group were calculated. The study characteristics of the included studies were presented in [Table 1].
Table 1: Characteristics of the studies evaluating the effects of glutathione S-transferase P1 A/G gene polymorphism on lung cancer risk

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Association of glutathione S-transferase P1 A/G gene polymorphism with lung cancer risk

In this meta-analysis, we found that GSTP1 G allele was associated with lung cancer risk (OR = 1.08, 95% CI: 1.02–1.14, P = 0.006; [Figure 1] and [Table 2]). Furthermore, the GG genotype was a risk factor for the lung cancer risk (OR = 1.09, 95% CI: 1.00–1.18, P = 0.04; [Figure 2] and [Table 2]). However, AA seemed not to play a protective role against the risk of lung cancer (OR = 0.94, 95% CI: 0.88–1.01, P = 0.09; [Figure 3] and [Table 2]).
Figure 1: Association between glutathione S-transferase P1 G allele and lung cancer susceptibility

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Table 2: Meta-analysis of the association of glutathione S-transferase P1 A/G gene polymorphism with risk of lung cancer

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Figure 2: Association between glutathione S-transferase P1 GG genotype and lung cancer susceptibility

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Figure 3: Association between glutathione S-transferase P1 AA genotype and lung cancer susceptibility

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In the subgroup analysis according to the ethnicity, this meta-analysis indicated that GSTP1 A/G gene polymorphism was not associated with lung cancer risk in Caucasians [Table 2].

However, in the subgroup analysis for Asian population, GSTP1 G allele was associated with lung cancer risk (OR = 1.15, 95% CI: 1.01–1.30, P = 0.03; [Table 2]). Furthermore, AA seemed to play a protective role against the risk of lung cancer (OR = 0.87, 95% CI: 0.78–0.96, P = 0.008; [Table 2]). However, GG genotype was not associated with lung cancer risk (OR = 1.25, 95% CI: 1.00–1.57, P = 0.05; [Table 2]).

Sensitivity analysis

Sensitivity analysis was also performed according to the source of the controls (healthy vs. hospital). The results from this sensitivity analysis of healthy were similar with those from nonsensitivity analysis, and the G allele/GG genotype was associated with the risk of lung cancer for overall populations [Table 3]. However, the results from this sensitivity analysis of hospital indicated that GSTP1 A/G gene polymorphism was not associated with lung cancer risk; and the relationship between G allele/GG genotype and lung cancer risk in overall populations was different from that from nonsensitivity analysis [Table 3].
Table 3: Meta-analysis of the association of glutathione S-transferase P1 A/G gene polymorphism with risk of lung cancer (sensitivity analysis)

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 > Discussion Top


In this meta-analysis, the association of GSTP1 G allele/GG genotype with the risk of lung cancer was observed in the overall populations. However, AA genotype was not associated with the onset of lung cancer in overall populations. In the subgroup analysis according to ethnicity, we found that GSTP1 G allele/AA genotype was associated with the risk of lung cancer. However, there was no an association between the GSTP1 A/G gene polymorphism with the risk of lung cancer in Caucasians.

Sensitivity analysis according to the source of the controls (healthy vs. hospital) was performed, and the results for GSTP1 from the sensitivity analysis using the studies using the healthy population as the control group were consistent with the nonsensitivity analysis. However, the result for GSTP1 G allele/GG genotype from the sensitivity analysis using the studies using the hospital nonlung cancer patients as the control group was inconsistent with the nonsensitivity analysis. We speculated that the G allele/GG genotype in hospital nonlung cancer patients might be significant that in healthy populations. However, more studies using should be conducted to explore this speculation.

In our previous meta-analysis,[3] we included 44 reports for the meta-analysis on the relationship between GSTP1 A/G gene polymorphism and lung cancer susceptibility, and reported that GSTP1 G allele is associated with the lung cancer susceptibility. In this meta-analysis, we included fifty reports for meta-analysis and found that G allele/GG genotype might be a significant factor to predict the risk of lung cancer. However, more original studies should be conducted to confirm it in further.

Our results indicated that an association between GSTP1 G allele/GG genotype and lung cancer risk was observed. However, the finding should be regarded cautiously because of many other ingredients, such as limited statistical power, were closely related to affect the results.


 > Conclusion Top


Our meta-analysis supports that GSTP1 G allele/GG genotype is associated with the risk of lung cancer. However, more association investigations are required to further clarify the association of GSTP1 A/G gene polymorphism with lung cancer risk.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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