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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 8  |  Page : 252-255

MicroRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility: A meta-analysis based on East Asian population


1 Department of Medical Gastroenterology, Cancer Hospital of Henan Province, The Affiliated Cancer Hospital of Zhengzhou University, Henan 450008, China
2 Department of Endoscopy Center, Cancer Hospital of Henan Province, The Affiliated Cancer Hospital of Zhengzhou University, Henan 450008, China
3 Department of General Surgery, Cancer Hospital of Henan Province, The Affiliated Cancer Hospital of Zhengzhou University, Henan 450008, China

Date of Web Publication17-Feb-2015

Correspondence Address:
Su-Xia Luo
Department of Medical Gastroenterology, Cancer Hospital of Henan Province, Henan 450003
China
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Source of Support: This work was supported by Henan Academy of medical science and technology projects(No.201203144), Conflict of Interest: None


DOI: 10.4103/0973-1482.151462

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 > Abstract 

Objective: The relationship between microRNA (miR-146a) rs2910164G/C polymorphism and gastrointestinal cancer susceptibility is not consistent with each other of the published articles. The aim of this meta-analysis was to acquire a more precise effect of the association between the miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer.
Materials and Methods: Through searching of the MedLine, Embase, China National Knowledge Infrastructure, and Wanfang databases. Case-control or cohort studies about the relationship between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility were screened and included in this meta-analysis. Quantitative data synthesis was conducted for the associations of miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer risk by statistical software STATA-11.0.
Results: Ten studies including 6473 gastrointestinal cancer patients and 7923 controls were identified and included in this meta-analysis. For recessive genetic model (CC vs. CG + GG), people with CG or GG is associated with the susceptibility of gastrointestinal cancer compared with genotype of CC (R = 0.73, 5% confidence interval [CI]: 0.55-0.97, [P = 0.03]); But for dominant model (CC + CG vs. GG) and homozygous model (CC vs. GG), no association of the miR-146a rs2910164G/C polymorphism and gastrointestinal cancer susceptibility were found (dominant: Odds ratio [OR] =0.94, 95% CI: 0.82-1.03, [P = 0.37]; homozygous: OR = 0.85, 95% CI: 0.71-1.03, [P = 0.10]). Sub-group analysis, for homozygous model, people with GG genotype had increased risk of developing colorectal cancer (OR = 0.77, 95% CI: 0.64-0.93, [P = 0.008]).
Conclusion: No significant association between miR-146a rs2910164G/C polymorphism and gastrointestinal cancer susceptibility was found in this meta-analysis. But for homozygous model, people with GG genotype may have increased risk of developing colorectal cancer.

Keywords: Gastrointestinal cancer, meta-analysis, microRNA-146a, polymorphism, susceptibility


How to cite this article:
Chen BB, Cao XG, Chen XB, Ma YJ, Deng WY, Li N, Huang JX, Luo SX, Zhao EJ. MicroRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility: A meta-analysis based on East Asian population. J Can Res Ther 2014;10, Suppl S4:252-5

How to cite this URL:
Chen BB, Cao XG, Chen XB, Ma YJ, Deng WY, Li N, Huang JX, Luo SX, Zhao EJ. MicroRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility: A meta-analysis based on East Asian population. J Can Res Ther [serial online] 2014 [cited 2020 Oct 29];10:252-5. Available from: https://www.cancerjournal.net/text.asp?2014/10/8/252/151462


 > Introduction Top


MicroRNAs (miRNAs/miR) are endogenous 18-24 nucleotide noncoding RNAs that could regulate gene expression and sequentially regulate various biological processes. [1] MiR-146 is a family of miR precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme dicer. [2] This sequence then associates with RNA-induced silencing complex which effects RNA interference. MiR-146 is primarily involved in the regulation of inflammation and other process that function in the innate immune system. [3] Recently, several studies reported the association of miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility with inconclusive conclusion. Hence, we perform this meta-analysis based on East Asian patients with published studies to further investigate this question.


 > Materials and methods Top


Literature search strategy

Relevant studies published before September 1 st , 2014 were identified through a search in MedLine, EMBASE, China National Knowledge Infrastructure and Wanfang databases. Case-control or cohort study about the relationship between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility were screened. The searching procedure was by two reviewers (Bei-Bei Chen amd Xin-Guang Cao) independently. The following items were used for searching the databases. "Genetic polymorphism" or "polymorphism" or "genetic variants" and "gastrointestinal cancer" or "gastric cancer" or "gastric carcinoma" or "stomach neoplasm" or "colorectal cancer" or "colon cancer" or "rectal cancer" and "miR-146a" or "miR-146a". The references used in eligible articles or textbooks were also reviewed to find other potential sources.

Inclusion and exclusion criteria

Studies included in this meta-analysis should meet the following criteria: (1) The study type should be case-control or cohort study; (2) the diagnosis of gastrointestinal cancer should be confirmed by pathology or cytology; (3) patients should be East Asian ethnicity; (4) the genotyping method should be correct; (5) sufficient data should be provided for calculate the odds ratio. The exclusion criteria were: (1) The review or case report study type; (2) duplicate published articles; (3) people of other ethnicity; (4) not enough data could be drawn from the original studies.

Data extraction

The data were extracted independently by two reviewers (Bei-Bei Chen and Su-Xia Luo). Disagreements were resolved by discussion. The following information was extracted from each included study: First author, year of publication, study population, ethnicity, number of GC cases and controls, frequency of genotypes, genotyping method, and P value for Hardy-Weinberg equilibrium.

Statistical analysis

The association between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility was measured by odds ratios (ORs) with 95% confidence interval (CI). The statistical significance of the pooled OR was examined by Z-test. Heterogeneities among the included studies were estimated using Cochran's Q-statistic with a P < 0.05 as statistically significant heterogeneity. All the statistical analyses were done by STATA-11.0 software (http://www.stata.com; Stata Corporation, College Station, TX).


 > Results Top


Characteristics of the included studies

According to the inclusion and exclusion criteria, 10 case-control studies including 6,473 gastrointestinal cancer patients and 7,923 controls were identified and finally included in this meta-analysis. All of the patients and controls were East Asian ethnicity. Of the included 10 studies, seven articles reported the association of miR-146a rs2910164 G/C polymorphism and gastric cancer susceptibility and three articles reported the association for colorectal cancer. Six studies are come from China, two from Japan and two from South Korea. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan-PCR are the two main genotyping methods for the including 10 studies. The general characteristics of the included 10 studies are shown in [Table 1] and [Table 2].
Table 1: The general characteristics of included studies for gastric cancer

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Table 2: The general characteristics of included studies for colorectal cancer

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Quantitative data synthesis

The association between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility was evaluated by the effects size of OR and its 95% CI. We first investigated the heterogeneity among the included studies for dominant recessive and homologous model. Significant heterogeneity among the studies was found for the above genetic models (all P < 0.05). Hence, the quantitative data synthesis was calculated by random effect model. For dominant (CC + CG vs. GG) and homozygous model (CC vs. GG), no association of the miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility were found (dominant: OR = 0.94, 95% CI: 0.82-1.03 [P = 0.37], [Figure 1]; homozygous: OR = 0.85, 95% CI: 0.71-1.03 [P = 0.10], [Figure 2]). For recessive genetic model (CC vs. CG + GG), people with CG or GG is associated with the susceptibility of gastrointestinal cancer compared with genotype (R = 0.73, 5% CI: 0.55-0.97, [P = 0.03]) [Figure 3].
Figure 1: The forest plot of odds ratios with a random-effects model for association microRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility under dominant model (CC + CG vs. GG)

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Figure 2: The forest plot of odds ratios with a random-effects model for association microRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility under homozygous model (CC vs. GG)

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Figure 3: The forest plot of odds ratios with a random-effects model for association microRNA-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility under recessive model (CC vs. CG + GG)

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Sub-group analysis

In sub-group analysis, for homozygous model, people with GG genotype had increased risk of developing colorectal cancer (OR = 0.77, 95% CI: 0.64-0.93, [P = 0.008]).

Publication bias

The publication bias for each genetic model was evaluated by Begg's funnel plot [Figure 4] and Egger's linear regression test. The shapes of the Begg's funnel plots seemed symmetric and did not reveal any evidence of obvious publication bias for all the genetic model [Figure 4]. Egger's line regression test indicated no statistical publication bias for all the genetic models (dominant, t = 1.09, P = 0.31; recessive model: t = 0.09, P = 0.93; homozygous model: t = 0.03, P = 0.974; heterozygous model: t = −0.58, P = 0.58), [Figure 4].
Figure 4: The Begg's funnel plots for evaluation the publication bias (a) Dominant model; (b) Recessive model; (c) Homologous model

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 > Disscusion Top


Gastrointestinal cancer was one of the most common diagnosed malignant carcinoma in the whole world. Gastrointestinal cancer, especially gastric and colorectal cancers, are a global epidemiological health concern. [14] It was estimated that 1,500,000 new cases of gastrointestinal cancer were diagnosed in the year of 2005, and a 2,110,000 new cases will be diagnosed in the year of 2025. [15] Like other solid malignant carcinomas, gastrointestinal cancer is also considered to be a kind of multifactorial disease induced by complex interactions between environmental and genetic factors. [16] The known risk factors associated with the gastrointestinal cancer were lifestyle, dietary, and other environmental exposures. And recently, many studies indicated that the genetic background such as genetic factors may also play an important role in the development of gastrointestinal cancer. [10] Recently, more and more evidence proved that single nucleotide polymorphism is associated the development of cancers including gastrointestinal carcinoma.

MicroRNA-146a was initially discovered during a systematic study aiming to identify miRNAs that play a potentially important role in the innate immune response to microbial infection. [17],[18] Recently, many miRs, including miR-146a, have been shown to contribute to the complex molecular mechanisms involved in the control of cell growth, differentiation and survival, processes mainly related to cancer development and progression. [17] MiR-146a existed of a common G/C polymorphism within the pre-miR-146a sequence which was proved to be important for its function. [19] Several articles reported the association between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer risk with inconclusive conclusion.

In this meta-analysis, we included 10 studies reporting an association between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer risk. The pooled results indicated that there was no significant association between miR-146a rs2910164 G/C polymorphism and gastrointestinal cancer susceptibility. But for homozygous model, people with GG genotype may have increased risk of developing colorectal cancer in East Asian population. But significant heterogeneity among the included studies made these results limited.

 
 > References Top

1.
Bartel DP, Chen CZ. Micromanagers of gene expression: The potentially widespread influence of metazoan microRNAs. Nat Rev Genet 2004;5:396-400.  Back to cited text no. 1
    
2.
Ambros V. microRNAs: Tiny regulators with great potential. Cell 2001;107:823-6.  Back to cited text no. 2
    
3.
Nurwidya F, Takahashi F, Takahashi, K. Meeting report: Current cancer perspectives from the 9 th Annual Meeting of the Japanese Society of Medical Oncology. Thorac Cancer 2012;3:94-7.  Back to cited text no. 3
    
4.
Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L, et al. Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 2010;16:3578-83.  Back to cited text no. 4
    
5.
Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, et al. Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter 2010;15:524-31.  Back to cited text no. 5
    
6.
Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, et al. Combined effect of miR-146a rs2910164 G/C polymorphism and Toll-like receptor 4+3725 G/C polymorphism on the risk of severe gastric atrophy in Japanese. Dig Dis Sci 2011;56:1131-7.  Back to cited text no. 6
    
7.
Zhou F, Zhu H, Luo D, Wang M, Dong X, Hong Y, et al. A functional polymorphism in Pre-miR-146a is associated with susceptibility to gastric cancer in a Chinese population. DNA Cell Biol 2012;31:1290-5.  Back to cited text no. 7
    
8.
Ahn DH, Rah H, Choi YK, Jeon YJ, Min KT, Kwack K, et al. Association of the miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G polymorphisms with gastric cancer risk and survival in the Korean population. Mol Carcinog 2013;52 Suppl 1:e39-51.  Back to cited text no. 8
    
9.
Ma B, Zheng JZ. microRNA-146a single nucleotide polymorphism and gastric cancer risk. Chin J Gerontol 2012;32:3150-2.  Back to cited text no. 9
    
10.
Song MY, Su HJ, Zhang L, Ma JL, Li JY, Pan KF, et al. Genetic polymorphisms of miR-146a and miR-27a, H. pylori infection, and risk of gastric lesions in a Chinese population. PLoS One 2013;8:e61250.  Back to cited text no. 10
    
11.
Min KT, Kim JW, Jeon YJ, Jang MJ, Chong SY, Oh D, et al. Association of the miR-146aC>G, 149C>T, 196a2C>T, and 499A>G polymorphisms with colorectal cancer in the Korean population. Mol Carcinog 2012;51 Suppl 1:e65-73.  Back to cited text no. 11
    
12.
Ma L, Zhu L, Gu D, Chu H, Tong N, Chen J, et al. A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population. Arch Toxicol 2013;87:825-33.  Back to cited text no. 12
    
13.
Lv M, Dong W, Li L, Zhang L, Su X, Wang L, et al. Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population. J Cancer Res Clin Oncol 2013;139:1405-10.  Back to cited text no. 13
    
14.
Lambert R, Hainaut P. The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer. Best Pract Res Clin Gastroenterol 2007;21:921-45.  Back to cited text no. 14
    
15.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 15
    
16.
Pharoah PD, Dunning AM, Ponder BA, Easton DF. Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 2004;4:850-60.  Back to cited text no. 16
    
17.
Labbaye C, Testa U. The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer. J Hematol Oncol 2012;5:13.  Back to cited text no. 17
    
18.
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006;103:12481-6.  Back to cited text no. 18
    
19.
Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2008;105:7269-74.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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