DOI: http://dx.doi.org/10.18203/2349-3933.ijam20150548

The relationship between pre-mir-146a G/C polymorphism and risk of gastric cancer in patients with gastric cancer in Ardabil province, Iran

Moradpour Hesari R., Damandan M., Hosseini-Asl S.

Abstract


Background: MicroRNAs (miRNAs)   are endogenous non-protein-coding short RNAs of 21-23 nucleotides (Kim, 2005; Bartel, 2004).polymorphism in human pre-mir-146a   has been recently implicated in human cancers. Gastric cancer (GC) is the most of common cancers, and is especially common in Ardabil province, located in North-West Iran. Single nucleotide polymorphism (SNP)is the most common type of genetic variation in the human genome .polymorphisms in human pre-mi RNA genome lesion modify the processing and/or target selection of human mi RNAs, which are implicated in cell cycle regulation , and thereby  play critical roles in carcinogenesis. Pre-mir-146a   G/C polymorphism designated rs2910164 is located on chromosome 5, in the stem region opposite to the mature pre-mir-146a sequence.

Methods: We performed a hospital-based, case-control study using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 individuals (50 gastric cancer patients and 50 age and sex matched cancer – free controls). The frequency of genotypes was 9(18%), 17(34%), and 24(48%) among cases and 3(6%), 14(28%), and 33(66%) among controls for C/C, G/C, and G/G, respectively. The 147bp amplified fragment was digested by Sac1 (Thermo science co.). An uncut fragment indicates allele G. However, substitution of C allele by G allele tends to create a Sac1 restriction site. Therefore, C allele is observed by 122bp and 25bp digested products. If the quantity of restriction enzyme used is inadequate, the homozygous may be detected as heterozygote, therefore, some sequenced samples were chosen for evaluating the accuracy of digestion. All the statistical analyses were performed using spss software.

Results: The frequencies of pre-miR-146a G/C genotypes in the case groups were significantly different from those in the control groups although clinically CC genotype in patients with gastric cancer incidence was higher than the control groups (18% versus 6%), so this difference was statistically significant (p=0.038).

Conclusions: In this study, between the polymorphism of G/C hsa-mir-146a and the risk of gastric cancer in Ardabil province, a significant relationship was found.


Keywords


Gastric cancer, Pre-mir-146a, Polymorphism, Ardabil

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References


Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. 2004;432(7014):235-240.

Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel M. D, Jarzab B, de la Chappelle A. Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer Proc. Natl. Acad. Sci. USA, 2009;106:1502–1505.

DiCioccio R. A, Odunsi K, Lele S. B, Zhao H. a functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis Carcinogenesis. 2008;29:1963–1966.

Hu J, Zacharek S, He Y. J, Lee H, Shumwa S, Duronio R. J, Xiong Y. WD40 protein FBW5 promotes ubiquitination of tumour suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Der. 2008;22(7): 866-871.

Xu T, Zhu Y, Wei Q. K, Yuan Y, Zhou F, Ge Y. Y, Yang J. R, Su H, Zhuang S. M. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis, 2008;29:2126–2131.

Guo H, Wan K, Xiong G, Hu H, Wang D, Xu X, Guan X, Yang K, Bai Y. A functional variant in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han Fam. Cancer, 2010;9:599–603.

Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Yonemura J, Ishizuka T, Arisawa T and Hirata I. Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population Helicobacter. 2010;15:524–531.

Zeng Y, Sun Q. M, Liu N. N, Dong G. H, Chen J, Yang L, Wang. Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population World J. Gastroenterol. 2010;16:3578–3583.

Akkiz H, Bayram S, Bekar A, Akgollu E, Uskudar O, Sandikci M. No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: A case-control study.2011;486:104-109.

Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, Hamajima N. 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;56:1131–1137.

Kim J. H, Cho A, Yin H, Schafer D. A, Mouneimne G, Simpson K.J, Nguyen K. V, Brugge, J. S, Montell, D. J. Psidin, a conserved protein that regulates protrusion dynamics and cell migration. 2011;25(7):730-741.

Wu M.N, Joiner W. J, Dean, T, Yue Z, Smith C. J, Chen D, Hoshi T, Sehgal A, Koh K. SLEEPLESS, a Ly-6/neurotoxin family member regulates the levels, localization and activity of Shaker. Nat. Neurosci. 2010;13(1):69-75.

Wang J, Bi J, Liu X, Li K, Di J, Wang B. Hsa-miR-146a polymorphism (rs2910164) and cancer risk: a meta-analysis of 19 case-control studies. Mol. Biol. Rep., 2012; 39:4571–4579.

Dong Wu, Fan Wang, Wei-Qi Dai, Lei He, Jie Lu, Ling Xu, Chuan-Yong Guo. The miR-146a rs2910164 G > C Polymorphism and Susceptibility to Digestive Cancer in Chinese. Asian Pacific J Cancer Prev, 14 (1): 399-403.

Permuth–Wey J, Thompson R. C, Burton Nabors L, Olson J. J, Browning J. E, Madden M. H, Ann Chen Y, Egan K. M. A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma J. Neurooncol. 2011;105:639–646.

Catucci I, Yang R, Verderio P, Pizzamiglio S, Heesen L, Hemminki K, Sutter C, Wappenschmidt B, Dick M, et al. Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases Hum. Mutat. 2010;31:E1052–1057.

Jazdzewski K, Murray E. L, Franssila K, Jarzab B, Schoenberg D. R. and de la Chapelle A. Common SNP in pre-miR-146a decreases mature Mir expression and predisposes to papillary thyroid carcinoma Proc. Natl. Acad. Sci. USA, 2008; 105:7269–7274.

Yue C, Wang M, Ding B, Wang W, Fu S, Zhou D, Zhang Z and Han S. Polymorphism of the pre-miR-146a is associated with risk of cervical cancer in a Chinese population .Gynecol. Oncol., 2011;122:33-7.