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Effects of Common Polymorphism rs11614913 in Hsa-miR-196a2 on Lung Cancer Risk  [PDF]
Zhengrong Yuan, Xu Zeng, Dan Yang, Weilu Wang, Zhihua Liu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061047
Abstract: Background Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the pathogenesis of lung cancer by altering the expression of tumor-related microRNAs. Several studies were investigated in recent years to evaluate the association between hsa-miR-196a2 rs11614913 polymorphism and increased/decreased lung cancer risk. In the present study, we performed a meta-analysis to systematically summarize the possible association. Methodology/Principal Findings We performed a meta-analysis of 4 case-control studies that included 2219 lung-cancer cases and 2232 cancer-free controls. We evaluated the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In the overall analysis, it was found that the rs11614913 polymorphism significantly elevated the risk of lung cancer (CC versus (vs.) TT OR = 1.26, 95% CI 1.07–1.49, P = 0.007; CC/CT vs. TT: OR = 1.13, 95% CI 0.98–1.29, P = 0.007; C vs. T: OR = 1.12, 95% CI 1.03–1.22, P = 0.008). In the subgroup analysis by ethnicity, statistically significantly increased cancer risk was found among Asians (CC vs. TT: OR = 1.30, 95% CI 1.10–1.54, P = 0.003; CT vs. TT: OR = 1.16, 95% CI 1.01–1.34, P = 0.039; CC vs. CT/TT: OR = 1.21, 95% CI 1.04–1.41, P = 0.012; C vs. T: OR = 1.14, 95% CI 1.05–1.25, P = 0.002). For Europeans, a significant association with lung cancer risk was found in recessive model (CC vs. CT/TT: OR = 0.63, 95% CI 0.40–0.98, P = 0.040). No publication bias was found in this study. Conclusions/Significance Our meta-analysis suggests that the rs11614913 polymorphism is significant associated with the increased risk of lung cancer, especially in Asians. Besides, the C allele of rs11614913 polymorphism may contribute to increased lung cancer risk.
Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies  [PDF]
Haiyan Chu,Meilin Wang,Danni Shi,Lan Ma,Zhizhong Zhang,Na Tong,Xinying Huo,Wei Wang,Dewei Luo,Yan Gao,Zhengdong Zhang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018108
Abstract: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results.
The Associations of Single Nucleotide Polymorphisms in miR-146a, miR-196a and miR-499 with Breast Cancer Susceptibility  [PDF]
Ping-Yu Wang, Zong-Hua Gao, Zhong-Hua Jiang, Xin-Xin Li, Bao-Fa Jiang, Shu-Yang Xie
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070656
Abstract: Background Previous studies have investigated the association between single nucleotide polymorphisms (SNPs) located in microRNAs (miRNAs) and breast cancer susceptibility; however, because of their limited statistical power, many discrepancies are revealed in these studies. The meta-analysis presented here aimed to identify and characterize the roles of miRNA SNPs in breast cancer risk, and evaluate the associations of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 with breast cancer susceptibility, respectively. Methodology/Principal Findings The PubMed and Embases databases were searched updated to 31st December, 2012. The complete data of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 from case-control studies for breast cancer were analyzed by odds ratios (ORs) with 95% confidence intervals (CIs) to reveal the associations of SNPs in miRNAs with breast cancer susceptibility. Totally, six studies for rs2910164 in miR-146a, involving 4225 cases and 4469 controls; eight studies for rs11614913 in miR-196a, involving 4110 cases and 5100 controls; and three studies of rs3746444 in miR-499, involving 2588 cases and 3260 controls, were investigated in the meta-analysis. The rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a decreased breast cancer susceptibility compared with the CC genotypes (OR = 0.906, 95% CI: 0.825–0.995, P = 0.039); however, no significant associations were observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast cancer susceptibility. Conclusions This meta-analysis demonstrates the compelling evidence that the rs11614913 CC genotype in miR-196a2 increases breast cancer risk, which provides useful information for the early diagnosis and prevention of breast cancer.
Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A Polymorphisms Are Associated with the Risk of Esophageal Cancer in a Chinese Population  [PDF]
Jun Yin, Xu Wang, Liang Zheng, Yijun Shi, Liming Wang, Aizhong Shao, Weifeng Tang, Guowen Ding, Chao Liu, Ruiping Liu, Suocheng Chen, Haiyong Gu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080570
Abstract: Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital based case–control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs) in the microRNAs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this study. The hsa-miR-34b/c rs4938723 T>C, pri-miR-124-1 rs531564 C>G, pre-miR-125a rs12975333 G>T and hsa-miR-423 rs6505162 C>A genotypes were determined using Ligation Detection Reaction (LDR) method. Our results demonstrated that hsa-miR-34b/c rs4938723 CC genotype had a decreased risk of ESCC. The association was evident among patients who never drinking. Hsa-miR-423 rs6505162 C>A might associated with a significantly increased risk of ESCC in patients who smoking. These findings indicated that functional polymorphisms hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A might alter individual susceptibility to ESCC. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations are required to confirm current findings.
Lack of Association between Hsa-miR-149 rs2292832 Polymorphism and Cancer Risk: A Meta-Analysis of 12 Studies  [PDF]
Lei Xu, Xin Zhou, Man-Tang Qiu, Rong Yin, Ya-Qin Wu, Lin Xu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073762
Abstract: Background MicroRNAs (miRNAs) participate in various cellular processes such as cell growth, differentiation, cell death and play an important role in a variety of diseases, especially in cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms (SNPs) on the hsa-miR-149 rs2292832 and susceptibility to cancer; however, the results remain inconclusive. Methodology/Principal Findings We carried out a meta-analysis of 12 studies including 5937 cases and 6081 controls from PubMed to assess the association between the hsa-miR-149 rs2292832 and cancer risk by pooled odds ratios (ORs) and 95% confidence intervals (CIs). However, our results showed that genotype distribution of the hsa-miR-149 rs2292832 was not associated with cancer risk in all genetic models. Subgroup analysis by cancer type, ethnicity or study design showed no significant association either. Conclusion Results of this meta-analysis suggest that the hsa-miR-149 rs2292832 polymorphism is not associated with cancer risk in spite of the potentially protective role of C allele in hepatocellular carcinoma and male gastric cancer.
Effects of Common Polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on Cancer Susceptibility: A Meta-Analysis  [PDF]
Wei Xu, Jijun Xu, Shifeng Liu, Bo Chen, Xueli Wang, Yan Li, Yun Qian, Weihong Zhao, Jianqing Wu
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020471
Abstract: Background MicroRNAs regulate gene expression at the post-transcriptional level and involved in diverse biological and pathological processes, including tumorigenesis. Rs11614913 in miR-196a2 and rs2910164 in miR-146a are shown to associate with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. Methodology/Principal Findings We assessed published studies of the association between these microRNA polymorphisms and cancer risk from eleven studies with 16,771 subjects for miR-196a2 and from ten studies with 15,126 subjects for miR-146a. As for rs11614913, the contrast of homozygote (TT vs CC: OR = 0.92, 95% CI = 0.85–0.99, Pheterogeneity = 0.45), allele (T vs C: OR = 0.96, 95% CI = 0.92–0.99, Pheterogeneity = 0.61) and recessive model (OR = 0.90, 95% CI = 0.84–0.97, Pheterogeneity = 0.50) produced statistically association. Subgroup analysis by ethnicity, statistically significantly decreased cancer risks were found among Asians for allele contrast (OR = 0.95, 95% CI = 0.90–0.99, Pheterogeneity = 0.74) and the recessive genetic model (OR = 0.90, 95% CI = 0.82–0.98, Pheterogeneity = 0.85). According to subgroup analysis by tumor types, the protective effect of C/T polymorphism was only found in breast cancer under allele contrast (T vs C: OR = 0.94, 95% CI = 0.88–0.99, Pheterogeneity = 0.26). For rs2910164, no significant associations were found among overall analysis model with relatively large heterogeneity. Through the stratified analysis, heterogeneity decreased significantly. In the subgroup analyses by cancer types, the C allele of rs2910164 was associated with protection from digestive cancer in allele contrast (C vs G: OR = 0.86, 95% CI = 0.77–0.96, Pheterogeneity = 0.51). Conclusions/Significance Our meta-analysis suggests that the rs11614913 most likely contributes to decreased susceptibility to cancer, especially in Asians and breast cancer. Besides, the C allele of the rs2910164 might be associated with a protection from digestive cancer.
Lack of Association of Two Common Polymorphisms rs2910164 and rs11614913 with Susceptibility to Hepatocellular Carcinoma: A Meta-Analysis  [PDF]
Zhongxia Wang, Yin Cao, Chunping Jiang, Guang Yang, Junhua Wu, Yitao Ding
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040039
Abstract: Background Single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the process of carcinogenesis by altering the expression of tumor-related microRNAs. It has been suggested that two common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association between the two SNPs and the risk for HCC. Methodology/Principal Findings We conducted a search of case-control studies on the associations of SNPs rs2910164 and/or rs11614913 with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, ScienceDirect, Wiley Online Library and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with the two polymorphisms was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). 5 studies on rs2910164 and 4 studies on rs11614913 were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distribution of the two polymorphisms was associated with risk for HCC in all genetic models. Similarly, subgroup analysis in Chinese population showed no association between the two SNPs and the susceptibility to HCC. Conclusions/Significance This meta-analysis suggests that two common SNPs rs2910164 and rs11614913 are not associated with the risk of HCC. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.
The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies  [PDF]
Bangshun He, Yuqin Pan, William C. Cho, Yeqiong Xu, Ling Gu, Zhenglin Nie, Liping Chen, Guoqi Song, Tianyi Gao, Rui Li, Shukui Wang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049032
Abstract: MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNA's properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.
Gene Polymorphisms of Micrornas in Helicobacter pylori-Induced High Risk Atrophic Gastritis and Gastric Cancer  [PDF]
Juozas Kupcinskas, Thomas Wex, Alexander Link, Marcis Leja, Indre Bruzaite, Ruta Steponaitiene, Simonas Juzenas, Ugne Gyvyte, Audrius Ivanauskas, Guntis Ancans, Vitalija Petrenkiene, Jurgita Skieceviciene, Limas Kupcinskas, Peter Malfertheiner
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087467
Abstract: Background and aims MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population. Methods Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR. Results Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR ?2.34, 95% CI 1.08–5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14–5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. Conclusions Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.
Different Effects of Three Polymorphisms in MicroRNAs on Cancer Risk in Asian Population: Evidence from Published Literatures  [PDF]
Yeqiong Xu, Ling Gu, Yuqin Pan, Rui Li, Tianyi Gao, Guoqi Song, Zhenlin Nie, Liping Chen, Shukui Wang, Bangshun He
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065123
Abstract: MicroRNAs (miRNAs) are a class of small non-protein-coding RNAs, which have emerged as integrated and important post-transcriptional regulators of gene expression. It has been demonstrated that single nucleotide polymorphisms (SNPs) exist in protein-coding genes. Accumulated studies have evaluated the association of miRNA SNPs with cancer risk, especially in Asian population, which included a series of related studies. However, the results remain controversial for the different genetic backgrounds, living habits and environment exposed. To evaluate the relationship between SNPs in miRNAs and cancer risk, 21 studies focused on Asian population were enrolled for the pooled analysis for three polymorphisms rs2910164, rs11614913, rs3746444 in three miRNAs miR-146aG>C, miR-196a2C>T, miR-499A>G using odds ratios (ORs) with 95% confidence intervals (CIs). For rs2910164 polymorphism, C allele was observed association with decreased overall cancer risk. In addition, subgroup analysis revealed of rs2910164 C allele decreased hepatocellular carcinoma (HCC), cervical cancer and prostate cancer risk among Chinese population. For rs11614913 polymorphism, TT genotype was observed to be associated with decreased cancer risk, especially for cancer type of colorectal cancer (CRC), lung cancer and country of Korea, North India. Whereas, rs3746444 G allele was an increased cancer risk factor in Chinese population, especially for breast cancer. In conclusion, this meta-analysis indicated that rs2910164 C allele was associated with decreased cancer risk in Chinese population. However, the association varied from different cancer types. Furthermore, TT genotype of rs11614913 was associated with decreased cancer risk. While different cancer types and countries contributed to different effects. Whereas, rs3746444 G allele was a risk factor in Chinese population, and the association varied from different cancer types.
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