Journal of Cancer Research and Therapeutics

ORIGINAL ARTICLE
Year
: 2015  |  Volume : 11  |  Issue : 5  |  Page : 97--100

The association between myeloperoxidase 463G>A polymorphisms and risk of lung cancer in East-Asia population


Xin Hou, Yuhua Gao, Yongjian Duan, Zhiwei Wang, Lei Shi, Jincheng Ma, Xuanhu Xie 
 Department of Oncology, The First Affiliated Hospital of Henan University, Henan, Kaifeng 475000, PR China

Correspondence Address:
Dr. Yongjian Duan
Department of Oncology, The First Affiliated Hospital of Henan University, Henan, Kaifeng 475000
PR China

Abstract

Objective: The association between the myeloperoxidase (MPO) 463 G>A polymorphism and lung cancer risk remains controversial. We perform this meta-analysis to further evaluate the MPO 463G>A polymorphism and lung cancer susceptibility. Materials and Methods: We performed the systemic literature search in PubMed, EMBASE, WANFANG, and CNKI databases for molecular epidemiologic studies on the association of MPO 463G>A polymorphism and lung cancer susceptibility. The pooled odds ratio (OR) of MPO 463G>A polymorphism and lung cancer risk were calculated by random or fixed effect model. Results: Seven case-control studies including 1538 lung cancer patients in the case group and 1673 healthy controls in the control group were included in this study. MPO 463G>A polymorphism was not associated with lung cancer susceptibility under the condition of recessive genetic model (AA vs. GG+GA) (OR = 0.69, P > 0.05) and homozygous genetic model (AA vs. GG) (OR = 0.65, P > 0.05). However, we found significantly decreased risk of lung cancer under dominant genetic model (GA+AA vs. GG) (OR = 0.84, P < 0.05). And no publication bias was found in this meta-analysis for the three genetic models (P > 0.05). Conclusion: This meta-analysis indicated that people with AA genetic type may have decreased lung cancer risk under dominant genetic model.



How to cite this article:
Hou X, Gao Y, Duan Y, Wang Z, Shi L, Ma J, Xie X. The association between myeloperoxidase 463G>A polymorphisms and risk of lung cancer in East-Asia population.J Can Res Ther 2015;11:97-100


How to cite this URL:
Hou X, Gao Y, Duan Y, Wang Z, Shi L, Ma J, Xie X. The association between myeloperoxidase 463G>A polymorphisms and risk of lung cancer in East-Asia population. J Can Res Ther [serial online] 2015 [cited 2022 Nov 26 ];11:97-100
Available from: https://www.cancerjournal.net/text.asp?2015/11/5/97/163854


Full Text

 INTRODUCTION



Lung cancer, also known as carcinoma of the lung or pulmonary carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. [1] Lung cancer is the leading cause of cancer-related death worldwide. It was reported that about 220,000 cases of lung cancer was diagnosed and 150,000 dead in the United States in the year of 2013. [2],[3] Lung cancer incidence was only inferior to prostate cancer for men and inferior to breast cancer in women. However, lung cancer is the leading cause of death in men and women. The exact reason and mechanism for lung cancer was not completely clear. Cigarette smoking is believed to be an important cause of lung cancer. About 90% lung cancer patients were smokers or past smokers. [4],[5] And other causes of lung cancer were radon gas exposure, asbestos exposure and others. Recently, some researchers have found that single-nucleotide polymorphism of some genes was also related to lung cancer. [6],[7],[8]

Myeloperoxidase (MPO) as an endogenous oxidant lysosomal enzyme available in polymorphonuclear neutrophils and monocytes catalyzes the reaction between the chloride ion and hydrogen peroxide and generates hypochlorous acid and other reactive oxygen species. [9] And MPO 463G>A polymorphism is considered to be associated with lung cancer susceptibility. But it was not conclusive.

 Materials and Methods



Search strategy

Studies related to the association between MPO 463G>A polymorphisms and risk of lung cancer in East-Asia population, published before March 2015, were identified by searching PubMed, EMBASE, CNKI, and WANFANG databases. The "nonsmall cell lung carcinoma/NSCLC/lung cancer/carcinoma of the lung", "MPO/myeloperoxidase", and "polymorphisms" were used as the free text word when searching the databases. The inclusion criteria are: lung cancer patients with histology or cytology conformation; the genotyping methods were polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan; all potentially relevant articles were assessed in full-text paper and all references of included articles were scanned for additional analysis according to the Cochrane Handbook for systematic reviews. [10]

Data extraction

Data of each included article were extracted by two reviewers (Hou Xin and Duan Yongjian) independently. If disagreement existed, the third reviewer was consulted for consensus. We extracted the general information and genotype distribution data. The general information include the name of the first author, the year of publication, country, genotyping methods, and Hardy-Weinberg equilibrium. The genotype distributions CC, CA, and AA in the case and control groups were carefully extracted and cross-checked.

Statistical analysis

All of the data were analyzed by Stata11.0 software (Stata Corporation, College Station, TX, USA). Dichotomous data were calculated as the odds ratio (OR) with the 95% confidence interval (CI). The statistical heterogeneity of the results across studies was evaluated by the Chi-square (χ2 ) test, [11] and the inconsistency was calculated by I2 . [12] If heterogeneity was found (I2 > 50%), the random-effect method (DerSimonian-Laird method) was applied to pool the data. If there was no significant heterogeneity, then the fixed-effect method was applied. The Begg's funnel plot was used to evaluate the possible publication bias.

 RESULTS



Description of included studies

Finally, seven case-control studies including 1538 lung cancer patients in the case group and 1673 healthy controls in the control group were included in this study. Three studies come from China, 3 from Korea, and 1 from Thailand. The genotyping methods are PCR-RFLP and TaqMan. Four studies reported the Hardy-Weinberg equilibrium and other three studies did not. The detailed information of the included studies were shown in [Table 1] and [Table 2].{Table 1}{Table 2}

Meta-analysis

We first evaluated the heterogeneity across the seven indicated studies. The results indicated that there was no statistical heterogeneity in the recessive (P = 0.33) homozygous genetic model (P = 0.21). However, significant heterogeneity in the dominant genetic model was exist (P = 0.01). The data were pooled by the fixed-effects model in the recessive and homozygous genetic models with OR = 0.69 (95% CI: 0.38-1.26) [Figure 1] and OR = 0.65 (95% CI: 0.36-1.18) [Figure 2], respectively. And for the dominant genetic model (GA+AA vs. GG), the OR and its 95% CI were pooled by random effect model (OR = 0.84, 95% CI: 0.71-0.99) [Figure 3].{Figure 1}{Figure 2}{Figure 3}

Publication bias

No evidence for publication bias was shown according to the shape of funnel plots [Figure 4], [Figure 5], [Figure 6].{Figure 4}{Figure 5}{Figure 6}

 DISCUSSION



The studies on the relationship between MPO 463G>A polymorphisms and risk of lung cancer in East-Asia were comparatively few, and the results of these studies are controversial. Hence, it is necessary to combine and analyze these data to find a conclusive result. Our purpose of this meta-analysis was to evaluate whether MPO 463G>A polymorphism increase or decrease the risk of developing lung cancer in East-Asia population.

MPO is a peroxidase enzyme that in humans is encoded by the MPO gene. MPO is most abundantly expressed in neutrophil granulocytes. Previously published studies indicated that MPO 463G>A polymorphism is associated with some type of cancers such as lung cancer, breast cancer and others. [8],[20] However, the results for some of the published articles were inconclusive. To further explicate this question, we performed this meta-analysis based on East-Asia population. We finally included seven case-control studies with 1538 lung cancer subjects in the case group and 1673 healthy controls in the control group. The pooled results showed that in recessive and homozygous genetic models, the OR were 0.69 (95% CI: 0.38-1.26) and 0.65 (95% CI: 0.36-1.18), respectively. And for the dominant genetic model (GA+AA vs. GG), the OR and its 95% CI was 0.84 (95% CI: 0.71-0.99). In recessive and homozygous genetic models, no association between MPO 463G>A polymorphisms and lung cancers risk was found in East-Asia population. But in dominant genetic model (GA+AA vs. GG), decreased lung cancer risk was observed in people with GA/AA genotype.

In this meta-analysis, several limitations were found. First, the number of subjects in several of the included articles was small which decreased the statistical power of this meta-analysis. Second, significant heterogeneity across the included studies was found in the dominant genetic model, which may decrease the stability of conclusion. Third, only studies published in English or Chinese were searched and included in this study.

In summary, this meta-analysis indicated that people with AA genetic type may have decreased lung cancer risk under the dominant genetic model. However, with a small number of case and controls in each study and significant heterogeneity among the articles, the conclusion of this meta-analysis was limited.

Financial support and sponsorship

This article was surported by The National Natural Science Fund (No. 81472745).

Conflicts of interest

There are no conflicts of interest.

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