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SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.

ABSTRACT: BACKGROUND:It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non-coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case-control study to address this issue. METHODS:Using the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type. RESULTS:We identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11-0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non-smokers (adjusted OR = 0.78, 95%CI: 0.62-0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03-2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study. CONCLUSION:The study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese.

SUBMITTER: Wang R

PROVIDER: S-EPMC6528608 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.

Wang Ruoyang R Feng Nannan N Wang Yu Y Gao Sumeng S Zhang Fangfang F Qian Ying Y Gao Ming M Yu Herbert H Zhou Baosen B Qian Biyun B

Journal of clinical laboratory analysis 20190413 4

<h4>Background</h4>It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non-coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case-control study to address this issue.<h4>Methods</h4>Using the TaqMan method, we genotyp ...[more]

PMID: 30980423

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Project description:Background Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism. Methods Chinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher’s exact test. The enriched pathways in each grade of tumors were also inferred. Results The study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein–Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors. Conclusion Patients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein–Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein–Barr virus, pathway analysis

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SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.

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SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.

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