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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 8  |  Page : 97-99

miR-146a rs2910164 polymorphism and the risk of colorectal cancer in Chinese population


1 Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China
2 Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China
3 Department of General Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, China

Date of Web Publication26-Mar-2018

Correspondence Address:
Zhansheng Zhu
Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu 221004
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.165864

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 > Abstract 


Objective: MicroRNAs-associated single nucleotide polymorphisms are thought to play an important role in cancer development. We investigated the association of miR-146a rs2910164 polymorphism with the risk of colorectal cancer (CRC) in Chinese population.
Materials and Methods: In this hospital-based case-control study of 560 cases and 780 age- and gender-matched healthy controls, the miR-146a rs2910164 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.
Results: We found that miR-146a rs2910164 polymorphism was not associated with CRC risk. However, the subgroup analysis by gender showed significant associations in male subjects (GG vs. CC: Odds ratios [OR] = 1.54, 95% confidence intervals [CI] = 1.04–2.29, P = 0.03; G vs. C: OR = 1.21, 95% CI = 1.01–1.45, P = 0.04).
Conclusion: Our study provides evidence that miR-146a rs2910164 polymorphism may play an important role in susceptibility to CRC in Chinese male population.

Keywords: Colorectal cancer, miR-146a, polymorphism, risk


How to cite this article:
Gao X, Zhu Z, Zhang S. miR-146a rs2910164 polymorphism and the risk of colorectal cancer in Chinese population. J Can Res Ther 2018;14, Suppl S1:97-9

How to cite this URL:
Gao X, Zhu Z, Zhang S. miR-146a rs2910164 polymorphism and the risk of colorectal cancer in Chinese population. J Can Res Ther [serial online] 2018 [cited 2019 Nov 19];14:97-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/8/97/165864




 > Introduction Top


Colorectal cancer (CRC) is one of the most common cancers in developed and developing countries, which is annually responsible for more than 500,000 deaths worldwide. Although the definite pathogenesis of CRC is still unknown, environmental factors and genetic susceptibility are believed to contribute to its onset.[1]

MicroRNAs (miRNAs) consist of ~22-nucleotide and belong to a class of highly conserved single-stranded RNAs that epigenetically regulate protein translation through binding to the 3' untranslated region of target messenger RNA and mediate either mRNA degradation or translational repression.[2] Some miRNA-associated single nucleotide polymorphisms (SNPs) have been reported to involve the development of cancer by influencing the biological function or expression level of miRNA.[3] Experimental evidence demonstrated that a common SNP (rs2910164), which located in the stem-loop of miR-146a precursor, had an influence on the mature miR-146a expression, and the presence of the rare C allele caused a less-efficient processing reaction in vitro and ultimately resulted in a decreased level.[4] Furthermore, the miR-146a rs2910164 polymorphism was associated with the risk of many cancer diseases, including bladder cancer, gastric cancer, and CRC.[3],[5],[6],[7],[8],[9] Although the association between miR-146a rs2910164 polymorphism and CRC had been reported in Chinese population, the total number of studies were small. Thus, we performed a hospital-based case-control study with 560 cases and 780 age- and gender-matched healthy controls to investigate the influence of miR-146a rs2910164 polymorphism on the risk of CRC in Chinese population.


 > Materials and Methods Top


Study population

Peripheral blood from a total of 560 CRC cases and 780 age- and gender-matched healthy controls were collected during the period from July 2012 to October 2014. All the participants were unrelated Chinese Han population. The diagnosis of CRC was based on preoperative colonoscopy, computed tomography scan, intraoperative exploration, and postoperative pathological examination. All individuals consented in writing to participate in the study. This study was approved by the medical ethics committee of the local hospital.

DNA extraction and genotyping

Genomic DNA of peripheral blood leukocytes was extracted using genomic DNA extraction kit (Qiagen). The miR-146a rs2910164 polymorphism was genotyped through the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. In brief, the primers used for amplifying DNA segments with the SNP site were 5'-CATGGGTTGTGTCAGTGTCAGAGCT-3' and 5'-TGCCTTCTGTCTCCAGTCTTCCAA-3'. The 25 μL PCR mixture consisted of 1 × reaction buffer, 2 mmol/L MgCl2, 0.25 mmol/L dNTPs, 1.5 units of Taq polymerase, and 0.3 μmol/L of each primer. The PCR profile contains an initial melting step of 4 min at 94°C, followed by 35 cycles of 30 s at 94°C, 30 s at 63°C, 30 s at 72°C, and a final elongation step of 4 min at 72°C. The PCR products were digested overnight at 37°C with 10 U of the specific restriction endonuclease Sac I, which cuts the C allele. To validate the genotyping result, a 10% random sample was reciprocally examined by different persons, and the reproducibility was 100%.

Statistical analysis

Student's t-tests and Chi-square tests were used to assess differences in the distributions of age and gender between cases and controls, respectively. The association between miR-146a rs2910164 polymorphism and the risk of CRC in Chinese population was estimated by calculating OR and 95% CI from logistic regression analyses. All statistical analyses were performed using Statistic Analysis System software (version 8.0, SAS Institute, Inc., Cary, North Carolina, USA).


 > Results Top


A total of 560 CRC cases and 780 age- and gender-matched healthy controls were genotyped for miR-146a rs2910164 polymorphism. The frequencies of smoking and nonsmoking were 46.4% and 53.6% in CRC cases, and 48.6% and 51.4% in the controls, respectively. The frequencies of drinking and nondrinking were 43.6% and 56.4% in CRC cases, and 39.2% and 60.8% in the controls, respectively [Table 1]. The genotype and allele frequencies of miR-146a rs2910164 polymorphism in the patients and controls are shown in the [Table 2]. The frequency of CC, GC, and GG genotype was 25.9% versus 28.2%, 50.9% versus 52.7%, and 23.2% versus 19.1% in CRC patients and control individuals, respectively. There was no significant difference in genotype and allele frequencies of miR-146a rs2910164 polymorphism between cases and control individuals (P > 0.05). However, stratified analysis by gender showed significant difference in genotype and allele frequencies. The miR-146a rs2910164 polymorphism was associated with CRC risk in male subjects (GG vs. CC: OR = 1.54, 95% CI = 1.04–2.29, P= 0.03; G vs. C: OR = 1.21, 95% CI = 1.01–1.45, P= 0.04).
Table 1: Distribution of selected characteristics among CRC cases and controls

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Table 2: Genotypic and allelic frequency of miR-146a rs2910164 polymorphism in CRC cases and controls

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 > Discussion Top


Many studies have identified miRNAs as vital regulatory molecules that may be involved in the pathogenesis of cancer.[10] One of these conserved miRNAs is miR-146a, which is well known for its important regulation of the immune response and inflammation. In addition, overexpression of miR-146a was observed in cancer, and associated with a worse survival rate for squamous cell lung cancer.[11],[12] Therefore, it is biologically plausible that genetic variations of the miR-146a gene may contribute to individual cancer susceptibility as genetic modifiers of cancer risk. A functional polymorphism (rs2910164) in miR-146a gene has been identified, and could affect the expression level of mature miR-146a.[13] Our case-control study demonstrated a significant association of the rs2910164 polymorphism in the pre-miR-146a gene with the susceptibility of CRC in a Chinese male population. Compared with male individuals carrying CC genotype or C allele, male individuals carrying GG genotype or G allele increased CRC risk.


 > Conclusion Top


Our study suggested that miR-146a rs2910164 polymorphism may contribute to the development of CRC in Chinese male population. However, these findings should be validated by well-designed studies.

Acknowledgment

This work was supported by the Natural Science Foundation of Jiangsu Province (Grants No. BK20140222).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Gao X, Huang M, Liu L, He Y, Yu Q, Zhao H, et al. Insertion/deletion polymorphisms in the promoter region of BRM contribute to risk of hepatocellular carcinoma in Chinese populations. PLoS One 2013;8:e55169.  Back to cited text no. 1
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Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004;116:281-97.  Back to cited text no. 2
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Wang M, Chu H, Li P, Yuan L, Fu G, Ma L, et al. Genetic variants in miRNAs predict bladder cancer risk and recurrence. Cancer Res 2012;72:6173-82.  Back to cited text no. 3
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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. 4
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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. 5
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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. 6
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Hu X, Li L, Shang M, Zhou J, Song X, Lu X, et al. Association between microRNA genetic variants and susceptibility to colorectal cancer in Chinese population. Tumour Biol 2014;35:2151-6.  Back to cited text no. 7
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Mao Y, Li Y, Jing F, Cai S, Zhang Z, Li Q, et al. Association of a genetic variant in microRNA-146a with risk of colorectal cancer: A population-based case-control study. Tumour Biol 2014;35:6961-7.  Back to cited text no. 8
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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. 9
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Ambros V. The functions of animal microRNAs. Nature 2004;431:350-5.  Back to cited text no. 10
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Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 2008;3:e2557.  Back to cited text no. 11
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Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, et al. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res 2009;69:5776-83.  Back to cited text no. 12
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Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 2008;29:2126-31.  Back to cited text no. 13
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  [Table 1], [Table 2]



 

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