Association between polymorphism in CDKN2B-AS1 gene and its interaction with smoking on the risk of lung cancer in a Chinese population.

BACKGROUND: Long non-coding RNAs became the hot spots in the carcinogenesis of various tumors. This case-control study evaluated the association between the rs2151280 in lncRNA CDKN2B-AS1 and lung cancer risk. METHODS: This study included 507 lung cancer patients and 542 healthy individuals. Odds ratios and their 95% confidence intervals were calculated by unconditional logistic regression analysis to evaluate the association between the rs2151280 and lung cancer risk. RESULTS: Compared with individuals carrying TT genotype, individuals carrying CC genotype of rs2151280 had a decreased risk of lung cancer (OR = 0.640, 95%CI = 0.421-0.972, P = 0.036). In the recessive model, rs2151280 CC genotype was observed to reduce the risk of lung cancer (OR = 0.684). C allele was associated with non-small cell lung cancer risk (OR = 0.674). The rs2151280 was significantly associated with lung adenocarcinoma risk (CCvsTT: OR = 0.567, 95%CI = 0.333-0.965, P = 0.037; CCvsTC+TT: OR = 0.543, 95%CI 0.330-0.893, P = 0.016, respectively). However, there was no significant association between rs2151280 and lung squamous cell carcinoma risk in five models. The quantitative analysis suggested that there were no significant interactions of rs2151280 with smoking exposure to lung cancer susceptibility. CONCLUSIONS: This hospital-based case-control study suggested that CDKN2B-AS1 rs2151280 T>C was associated with the risk of lung cancer.

Polymorphism in lncRNA AC016683.6 and its interaction with smoking exposure on the susceptibility of lung cancer.

BACKGROUND: Long non-coding RNAs play pivotal roles in the carcinogenesis of multiple types of cancers. This study is firstly to evaluate influence of rs4848320 and rs1110839 polymorphisms in long non-coding RNA AC016683.6 on the susceptibility of lung cancer. METHODS: The present study was a hospital-based case-control study with 434 lung cancer patients and 593 cancer-free controls. Genotyping of the two SNPs detected by Taqman® allelic discrimination method. RESULTS: There were no statistically significant associations between rs4848320 and rs1110839 polymorphisms in AC016683.6 and risk of lung cancer in overall population. However, in the smoking population, rs4848320 and rs1110839 polymorphisms significantly increased the risk of lung cancer in dominant and homozygous models (Rs4848320: P = 0.029; Rs1110839: P = 0.034), respectively. In male population, rs1110839 genetic variant was related to the risk of lung cancer in all genetic models (GG vs. TT: P = 0.008; Dominant model: P = 0.029; Recessive model: P = 0.027) rather than heterozygous model. The crossover analyses provided rs4848320 and rs1110839 risk genotypes carriers combined with smoking exposure 2.218-fold, 1.755-fold increased risk of lung cancer (Rs4848320: P = 0.005; Rs1110839: P = 0.017). Additionally, there were significantly positive multiplicative interaction of rs4848320 polymorphism with smoking status, with adjusted OR of 2.244 (1.162-4.334), but rs1110839 polymorphism did not exist. CONCLUSIONS: Rs4848320 and rs1110839 polymorphisms may be associated with lung cancer susceptibility. Interaction of rs4848320 risk genotypes with smoking exposure may strengthen the risk effect on lung cancer.

Clinicopathological and prognostic significance of long noncoding RNA MALAT1 in human cancers: a review and meta-analysis.

BACKGROUND: The aberrant regulation of MALAT1 has been indicated to be involved in various carcinogenic pathways contributing to the tumourigenesis and progression of cancers. The current meta-analysis summarized the research advances of MALAT1 functions and analyzed its prognostic value among multiple types of cancers. METHODS: Eligible studies were identified through retrieving the PubMed, Web of Science, and CNKI databases, up to Mar 1, 2018. 28 studies of 5436 patients and 36 studies of 3325 patients were enrolled in the meta-analysis to evaluate the association of MALAT1 expression with survival outcomes and clinical parameters. RESULTS: The results demonstrated that over-expression of MALAT1 may predict lymph node metastasis (pooled OR = 2.335, 95% CI 1.606-3.395, P = 0.000) and distant metastasis (pooled OR = 2.456, 95% CI 1.407-4.286, P = 0.002). Moreover, MALAT1 was also related with tumour size (pooled OR = 1.875, 95% CI 1.257-2.795, P = 0.002) and TNM stage (pooled OR = 2.034, 95% CI 1.111-3.724, P = 0.021). Additionally, elevated MALAT1 expression could predict poor OS (pooled HR = 2.298, 95% CI 1.953-2.704, P = 0.000), DFS (pooled HR = 2.036, 95% CI 1.240-3.342, P = 0.005), RFS (pooled HR = 2.491, 95% CI 1.505-4.123, P = 0.000), DSS (pooled HR = 2.098, 95% CI 1.372-3.211, P = 0.001) and PFS (pooled HR = 1.842, 95% CI 1.138-2.983, P = 0.013) in multivariate model. Importantly, subgroup analyses disclosed that increased MALAT1 expression had a poor OS among different cancer types (Estrogen-dependent cancer: pooled HR = 2.656, 95% CI 1.560-4.523; urological cancer: pooled HR = 1.952, 95% CI 1.189-3.204; glioma: pooled HR = 2.315, 95% CI 1.643-3.263; digestive cancer: pooled HR = 2.451, 95% CI 1.862-3.227). CONCLUSIONS: The present findings demonstrated that MALAT1 may be a novel biomarker for predicting survival outcome, lymph node metastasis and distant metastasis.

Long non-coding RNA HOTAIR polymorphism and susceptibility to cancer: an updated meta-analysis.

BACKGROUND: An increasing number of publications are drawing attention to the associations between six common polymorphisms in HOX transcript anti-sense RNA (HOTAIR) and the risk of cancers, while these results have been controversial and inconsistent. We conducted an up-to-date meta-analysis to pool eligible studies and to further explore the possible relationships between HOTAIR polymorphisms (rs920778, rs7958904, rs12826786, 4,759,314, rs874945, and rs1899663) and cancer risk. METHODS: A systematic retrieval was conducted up to 1 July 2017 in the PubMed, Web of Science, and CNKI databases. Eighteen eligible publications including 45 case-control studies with 58,601subjects were enrolled for assessing the associations between the 6 polymorphisms in HOTAIR and cancer risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed to reveal the polymorphisms and susceptibility to cancer. All the statistical analyses were performed using STATA 11.0 software. RESULTS: The pooled analyses detected significant associations between the rs920778 polymorphism and increased susceptibility to cancer in recessive, dominant, allelic, homozygous, and heterozygous models. For the rs7958904 polymorphism, we obtained the polymorphism significantly decreased susceptibility to overall cancer risk among five genetic models rather than recessive and homozygous models. For the rs12826786 polymorphism, we identified it significantly increased susceptibility to cancer risk in all genetic models rather than heterozygous models. However, no significant association was found between the rs1899663, rs874945, and rs4759314 polymorphisms and susceptibility of cancer. CONCLUSION: These findings of the meta-analysis suggest that HOTAIR polymorphism may contribute to cancer susceptibility.

The Polymorphisms of lncRNA HOXA11-AS and the risk of Lung Cancer in Northeastern Chinese population.

Long non-coding RNAs (LncRNA) have been wildly explored in several malignant tumors. This study aimed to evaluate the effect of HOXA11-AS polymorphisms (rs17427875 and rs11564004) on lung cancer susceptibility and its interaction with smoking exposure. This hospital-based case-control study, which included 466 cases and 557 controls, was carried out in Shenyang City, Liaoning province. The genotyping method was TaqMan allelic discrimination assay and all statistical analysis were performed by SPSS 20.0 and R (3.5.3). The results demonstrated that HOXA11AS-rs17427875 polymorphisms were correlated with the susceptibility of lung adenocarcinoma. T alleles of rs17427875 played a portal role in increasing lung adenocarcinoma risk. HOXA11AS-rs11564004 polymorphisms had the significant association with lung cancer risks, as well as its subtypes like non-small cell lung cancer, adenocarcinoma. The allele G of rs11564004 acted as a protective factor for lung cancer. The similar results were observed in the homozygous model and recessive model of rs11564004. Nevertheless, interaction analysis of the additive and multiplicative model scales showed no statistical significance between HOXA11-AS polymorphisms and smoking exposure in the development of lung cancer.

Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

Lung cancer is a leading cause of cancer death all around the world. Long non-coding RNAs (lncRNAs) have been confirmed to be involved in carcinogenesis of malignancies. However, the molecular mechanism of most lncRNAs in various kinds of cancers remains unclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role in non-small cell lung cancer, and the overexpression of HNRNPA1 is shown to promote the proliferation of lung adenocarcinoma cells. In our study, we find that the overexpression of HOTAIR could promote the proliferation and overexpression of miR-149-5p could inhibit the proliferation of lung cancer cells. Flow cytometric analysis determines that overexpression of miR-149-5p induces cell cycle arrest in the G0/G1 phases, whereas overexpression of HOTAIR decreases the proportion of G0/G1phase cells. Also, overexpression of HOTAIR promotes the migration and invasion ability of lung cancer cells, confirmed by the wound-healing and transwell assays, which are suppressed by overexpression of miR-149-5p. Furthermore, the dual-luciferase reporter assay indicates that miR-149-5p could bind both HOTAIR and the 3'UTR of HNRNPA1. In summary, we find that HOTAIR can regulate HNRNPA1 expression through a ceRNA mechanism by sequester miR-149-5p, which post-transcriptionally targets HNRNPA1, thus promoting lung cancer progression.

Polymorphisms in the PVT1 Gene and Susceptibility to the Lung Cancer in a Chinese Northeast Population: a Case-control Study.

Background: Long non-coding RNA (lncRNA) PVT1 has been identified to be related to risk of a variety of cancers, such as gastric cancer, pancreatic cancer and follicular lymphoma. This study assesses the association between genetic polymorphisms of PVT1 and the susceptibility to lung cancer as well as gene-environmental interaction. Method: A hospital-based case-control study, including 515 lung cancer patients and 582 healthy controls, was carried out in Shenyang, China. Unconditional logistic regression analyses calculated the odds ratios (ORs) and their 95% confidence intervals (CIs) to assess the associations between polymorphisms of rs2608053, rs1561927, rs13254990 and susceptibility to lung cancer. The gene-environment interaction was evaluated by additive model and multiplicative model. Results: There were no statistically significant associations between rs2608053 and rs1561927 polymorphisms in PVT1 and risk of lung cancer in the overall population. The relationship between polymorphism rs13254990 in PVT1 gene and lung adenocarcinoma was significant. Composed with individuals carrying CC genotypes, TT genotype carriers were more likely to develop lung adenocarcinoma (adjusted OR=2.095; 95%CI=1.084-4.047, P=0.028). In the recessive model, it also showed a statistically significant difference (TT vs CT+CC: adjusted OR=2.251, 95%CI=1.174-4.318, P=0.015). In nonsmokers, individuals carrying genotype CT had a lower risk of lung cancer than those with CC genotype (adjusted OR=0.673, 95%CI=0.472-0.959, P=0.028). Comparing with the homozygous CC, the patients with the heterozygous CT had a lower risk of NCSLC in the non-smoking group (adjusted OR =0.685, 95%CI=0.477-0.984, P=0.040). Additionally, gene-environment interaction results were not statistically significant in either additive model or multiplicative model. Conclusion: The polymorphism rs13254990 in PVT1 gene is associated with the risk of lung adenocarcinoma in a Chinese northeast population.

LncRNA NEAT1 polymorphisms and lung cancer susceptibility in a Chinese Northeast Han Population: A case-control study.

BACKGROUND: Long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is a novel lncRNA localized specifically to nuclear paraspeckles. The study analyses the association between NEAT1 genetic polymorphisms and the susceptibility of lung cancer in a Chinese Northeast Population. METHODS: The NEAT1 rs512715 and rs2239895 genetic polymorphisms were genotyped in 462 lung cancer cases and 559 controls by a Real-Time Polymerase Chain Reaction (PCR) with the TaqMan discrimination assay. RESULTS: Our study found that the polymorphisms of two SNPs increased or decreased the risk of lung cancer were not obvious, but statistical significance in non-small cell lung cancer and lung squamous cell carcinoma can be observed. Compared with homozygous CC genotype carriers, the GC genotype of rs2239895 was positively related to the risk of lung squamous cell carcinoma (OR 1.805, 95% CI, 1.168-2.789, P = 0.008). Similarly, associations between rs2239895 and lung squamous cell carcinoma risk were found (CC + GC vs. GG, OR 1.668, 95%CI, 1.093-2.545, P = 0.018) in dominant model. In stratified analysis for age, rs2239895 GC genotype was observed to increase the risk of non-small-cell lung cancer compared with CC genotype (OR 1.562, 95%CI, 1.029-2.371, P = 0.036). However, the study showed that negative correlation the lung cancer risk and rs512715 polymorphisms. There was no remarkable relationship between the both additive and multiplicative model about the two SNPs. CONCLUSIONS: The polymorphisms rs2239895 were associated with the risk of lung squamous cell carcinoma. The interaction between the two SNPs and the cigarette smoking was no notable difference.

Polymorphisms in Long Noncoding RNA-Prostate Cancer-Associated Transcript 1 Are Associated with Lung Cancer Susceptibility in a Northeastern Chinese Population.

Long noncoding RNAs (lncRNAs) are a new class of potential biomarkers and therapeutic targets for cancer. In this study, we chose four single nucleotide polymorphisms (SNPs) in lncRNA-PCAT1 (rs1026411 G>A, rs12543663 A>C, rs710886 T>C, and rs16901904 T>C) to investigate the association between genetic variant in lncRNA-PCAT1 and susceptibility to lung cancer. The study was a hospital-based case-control study including 561 cancer-free controls and 468 lung cancer cases. Genotyping of four SNPs was conducted by using Taqman® allelic discrimination methods. All statistical analyses were performed by using IBM SPSS Statistics 22 software. We failed to find significant associations between four SNPs and lung cancer risk in all models. However, polymorphisms in rs1026411 and rs710886 were observed to have significant associations with susceptibility to non-small cell lung cancer (AG vs. GG: odds ratio [OR]a = 0.701, p* = 0.020 and AA+AG vs. GG: ORa = 0.711 [superscript "a" refers to OR adjusted by age, gender, and smoking], p* = 0.017 [asterisks "*" refers to p adjusted by age, gender, and smoking] for rs1026411; CT vs. TT: ORa = 0.723, p* = 0.047 and CC+CT vs. TT: ORa = 0.729, p* = 0.038 for rs710886). Besides, the rs1026411 polymorphism had a similar association with lung adenocarcinoma risk (AG vs. GG: ORa = 0.663, p* = 0.019 and AA+AG vs. GG: ORa = 0.685, p* = 0.020). Polymorphisms in rs710886 and rs16901904 were observed to be associated with lung squamous cell carcinoma risk (CC+CT vs. TT: ORa = 0.638, p* = 0.040 for rs710886; CC vs. TT: ORa = 2.582, p* = 0.033 and CC vs. TT+CT: ORa = 2.381, p* = 0.048 for rs16901904). In addition, there were no significant results in gene-environmental interactions in both additive and multiplicative models. Our results suggested that polymorphisms in lncRNA-PCAT1 might be associated with lung cancer susceptibility in a northeastern Chinese population. The results of gene-environmental interactions were not significant in lung cancer.

Diagnostic performance of circular RNAs in human cancers: A systematic review and meta-analysis.

BACKGROUND: Recently, accumulating evidence have revealed that circular RNA (circRNA) was deregulated in multiple types of cancer, suggesting that circRNA might serve as a novel candidate biomarker of cancer diagnosis. However, inconsistent results have become an obstacle in applying circRNAs to clinical practice. The aim of this study is to evaluate diagnostic value of circRNAs among cancers. METHODS: A literature search was systematically performed among PubMed, Sciencedirect, Cochrane Library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases up to February 15, 2019. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratios, negative likelihood ratios, diagnostic odds ratio, and area under the SROC curve (AUC) were applied to evaluate diagnostic performance of circRNAs. RESULTS: In total, the study included 64 studies with single circRNA and 13 studies with combined circRNAs. Overall, the study presented that a single circRNA had moderate diagnostic value, with a SEN of 0.75, a SPE of 0.76, and an AUC of 0.82. The plasma circRNAs had higher diagnostic accuracy than tissue (AUC: 0.87, 95% confidence interval [CI]: 0.83-0.89 for plasma/serum subgroup; AUC: 0.79, 95% CI: 0.75-0.82 for tissue subgroup). Furthermore, the combined circRNAs had good diagnostic efficacy for GC, with a SEN of 0.89, a SPE of 0.94, and an AUC of 0.97, respectively. CONCLUSION: This study confirmed that circRNAs may be candidate biomarkers for cancer diagnosis. In particular, diagnosis of combined circRNAs will be a new alternative applied to clinical research and practice for cancer.

Polymorphism in lncRNA AC008392.1 and its interaction with smoking on the risk of lung cancer in a Chinese population.

PURPOSE: To evaluate the association between rs7248320 in lncRNA AC008392.1 and the risk of lung cancer, this case-control study was carried out in a Chinese population. This study also evaluated the gene-environment interaction between rs7248320 and exposure to smoking status on the risk of lung cancer. PATIENTS AND METHODS: We conducted a hospital-based case-control study including 512 lung cancer cases and 588 healthy controls. The association between rs7248320 and the risk of lung cancer was analyzed, and the gene-environment interaction was estimated on an additive scale. RESULTS: The variant genotype of rs7248320 was significantly related to the risk of non-small-cell lung cancer (NSCLC). Individuals carrying homozygous GG genotype had decreased risk of NSCLC, compared with individuals carrying the homozygous wild AA genotype/heterozygote GA genotype (adjusted odds ratio [OR] =0.653, 95% confidence interval [CI] =0.442-0.966, P=0.033). Moreover, in the subgroup of ages, there were statistically significant associations between rs7248320 and the risk of lung cancer and NSCLC in the population over 60 years of age. Compared with individuals carrying genotypes AA/GA, individuals with genotype GG had the lower risk of lung cancer and NSCLC (adjusted ORs were 0.579 and 0.433, 95% CIs were 0.338-0.994 and 0.231-0.811, P-values were 0.048 and 0.009, respectively). Compared with homozygote AA, the homozygote GG was associated with a decreased risk in NSCLC (OR =0.456, 95% CI =0.235-0.887, P=0.021). There were no statistically significant results in gene-environment interactions on an additive scale. CONCLUSION: These findings suggest that lncRNA AC008392.1 rs7248320 may be involved in genetic susceptibility to NSCLC in a Chinese population.

Genetic variants in lncRNA HOTAIR are associated with lung cancer susceptibility in a Chinese Han population in China: a case-control study.

PURPOSE: HOX transcript antisense RNA (HOTAIR) plays important roles in carcinogenesis of various kinds of malignant tumors, including lung cancer. Single nucleotide polymorphisms (SNPs) in HOTAIR were reported to be associated with susceptibility of several kinds of cancers. The present study assessed the associations between three SNPs (rs4759314, rs12826786, and rs920778) and lung cancer susceptibility, as well as gene-environment interaction between smoking exposure and the polymorphisms. PATIENTS AND METHODS: A case-control study including 551 patients and 543 healthy controls was performed. The associations between SNPs and lung cancer susceptibility were assessed by logistic regression model. RESULTS: rs4759314 was observed to increase the susceptibility of lung cancer, lung adenocarcinoma, squamous lung cancer, and small cell lung cancer statistically significantly (OR of 4.048 for lung cancer; 3.584 for lung adenocarcinoma; 4.671 for squamous lung cancer; 4.502 for small cell lung cancer). In stratified analysis for sex and smoking exposure, rs4759314 GG and AG genotype was also observed to increase the risk of lung cancer statistically significantly (OR of 5.221 for male; 3.491 for female; 3.653 for nonsmoking individuals; 4.458 for smoking individuals). Results of gene-environment interaction analysis showed that there was no interaction between smoking exposure and rs4759314 on additive scale. Results of logistic regression model suggested that the interaction between smoking and rs4759314 was statistically significant on multiplicative scale. rs12826786 CT genotype carriers and T allele could decrease the risk of developing lung cancer (OR of 0.751 for CT carriers; 0.785 for T allele), and in dominant model, TC and TT genotype carriers also have a 0.249-fold decrease risk compared with CC genotype carriers. In stratified analysis for smoking exposure, TC and TT have a 0.432-fold decreased risk compared with CC genotype carriers. CONCLUSION: HOTAIR rs4759314 and rs12826786 were associated with lung cancer susceptibility in Chinese Han population.

Association Between Long Noncoding RNA MEG3 Polymorphisms and Lung Cancer Susceptibility in Chinese Northeast Population.

Long noncoding RNA (lncRNA) maternal-expressed gene 3 (MEG3) is associated with proliferation of various tumor cells and has decreased expression in many types of cancers. In this study, we aimed at demonstrating the association between MEG3 polymorphisms and the risk of lung cancer in northeast China. There were 526 lung cancer patients and 526 healthy controls included in this hospital-based case-control study. The genotyping of two polymorphisms, rs7158663 G > A and rs4081134 G>A, was performed by the Taqman allelic discrimination method. We found that MEG3 rs4081134-AA may be associated with the risk of lung cancer (AA vs. GG: adjusted odds ratio [OR] = 0.487, confidence interval [95% CI] = 0.257-0.897, p = 0.030; AA vs. AG+GG: adjusted OR = 0.522, 95% CI = 0.274-0.992, p = 0.047). Similar associations in several subgroups were found in subsequent stratified analysis. Further, there were no statistically significant interactions of rs4081134 polymorphism and smoking to lung cancer susceptibility. In addition, the associations between the MEG3 rs7158663 polymorphism and lung cancer susceptibility were not found. These results indicate that the MEG3 rs4081134 polymorphism was significantly associated with lung cancer susceptibility in the Chinese population.