Genetic variants in circTUBB interacting with smoking can enhance colorectal cancer risk
Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However...
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Published in | Archives of toxicology Vol. 94; no. 1; pp. 325 - 333 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
2020
Springer Nature B.V |
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Abstract | Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. The MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1150 cases and 1342 controls) and two European populations (9023 cases and 386,896 controls) using logistic regression analysis. Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44–2.21,
P
= 1.42 × 10
–7
,
P
FDR
= 2.80 × 10
–5
] and even reached significance in a genome-wide association study (GWAS) under the dominant model (
P
= 1.28 × 10
–8
). Similar results were found in the European populations (OR
meta
= 1.30, 95% CI = 1.10–1.53). Both stratification and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk (
P
interaction
= 1.48 × 10
–2
). Here, we first comprehensively identified genetic variants in MREs of CRC-circRNAs and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for a comprehensive understanding of colorectal cancer etiology. |
---|---|
AbstractList | Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. The MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1150 cases and 1342 controls) and two European populations (9023 cases and 386,896 controls) using logistic regression analysis. Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44-2.21, P = 1.42 × 10
, P
= 2.80 × 10
] and even reached significance in a genome-wide association study (GWAS) under the dominant model (P = 1.28 × 10
). Similar results were found in the European populations (OR
= 1.30, 95% CI = 1.10-1.53). Both stratification and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk (P
= 1.48 × 10
). Here, we first comprehensively identified genetic variants in MREs of CRC-circRNAs and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for a comprehensive understanding of colorectal cancer etiology. Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. The MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1150 cases and 1342 controls) and two European populations (9023 cases and 386,896 controls) using logistic regression analysis. Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44–2.21, P = 1.42 × 10 –7 , P FDR = 2.80 × 10 –5 ] and even reached significance in a genome-wide association study (GWAS) under the dominant model ( P = 1.28 × 10 –8 ). Similar results were found in the European populations (OR meta = 1.30, 95% CI = 1.10–1.53). Both stratification and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk ( P interaction = 1.48 × 10 –2 ). Here, we first comprehensively identified genetic variants in MREs of CRC-circRNAs and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for a comprehensive understanding of colorectal cancer etiology. Circular RNAs (circRNAs) are an intriguing class of regulatory RNAs involved in the tumorigenesis of many cancers, including colorectal cancer. Mechanistically, circRNAs sponge microRNAs (miRNAs) with specific miRNA response elements (MREs) and compete for regulatory target genes downstream. However, the genetic effects of MREs on colorectal cancer susceptibility remain unclear. The MREs of colorectal cancer-associated circRNAs (CRC-circRNAs) and corresponding single nucleotide polymorphisms (SNPs) were identified by the transcriptome of cancer cells and the 1000 Genomes Project. The association between candidate SNPs and colorectal cancer risk was evaluated in a Chinese population (1150 cases and 1342 controls) and two European populations (9023 cases and 386,896 controls) using logistic regression analysis. Among the 197 candidate SNPs within MREs of 186 CRC-circRNAs, rs25497 in circTUBB was significantly associated with colorectal cancer risk in a Chinese population after false discovery rate (FDR) correction [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.44–2.21, P = 1.42 × 10–7, PFDR = 2.80 × 10–5] and even reached significance in a genome-wide association study (GWAS) under the dominant model (P = 1.28 × 10–8). Similar results were found in the European populations (ORmeta = 1.30, 95% CI = 1.10–1.53). Both stratification and interaction analyses revealed that rs25497 interacting with smoking affected the colorectal cancer risk (Pinteraction = 1.48 × 10–2). Here, we first comprehensively identified genetic variants in MREs of CRC-circRNAs and evaluated their effects on colorectal cancer risk in both Chinese and European populations. These findings provide basis for a comprehensive understanding of colorectal cancer etiology. |
Author | Zhang, Ke Li, Shuwei Zheng, Rui Shu, Yongqian Meng, Yixuan Du, Mulong Wang, Meilin Ben, Shuai Xin, Junyi Liu, Lingxiang Chu, Haiyan Zhang, Zhengdong Xu, Kaili Gu, Dongying |
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Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 5 givenname: Rui surname: Zheng fullname: Zheng, Rui organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 6 givenname: Junyi surname: Xin fullname: Xin, Junyi organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 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Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 9 givenname: Haiyan surname: Chu fullname: Chu, Haiyan organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 10 givenname: Zhengdong surname: Zhang fullname: Zhang, Zhengdong organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 11 givenname: Yongqian surname: Shu fullname: Shu, Yongqian organization: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University – sequence: 12 givenname: Mulong surname: Du fullname: Du, Mulong email: drdumulong@njmu.edu.cn organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University – sequence: 13 givenname: Lingxiang surname: Liu fullname: Liu, Lingxiang email: llxlau@163.com organization: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University – sequence: 14 givenname: Meilin orcidid: 0000-0002-4996-958X surname: Wang fullname: Wang, Meilin email: mwang@njmu.edu.cn organization: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31797002$$D View this record in MEDLINE/PubMed |
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Keywords | Genetic variants circTUBB Interaction Colorectal cancer |
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SubjectTerms | Aged Asian Continental Ancestry Group - genetics Biomedical and Life Sciences Biomedicine Cancer Case-Control Studies Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Confidence intervals Environmental Health Etiology European Continental Ancestry Group - genetics Female Gene expression Gene Expression Regulation, Neoplastic Genetic diversity Genetic effects Genetic Predisposition to Disease Genetic variance Genome-wide association studies Genome-Wide Association Study Genomes Genotoxicity and Carcinogenicity Health risk assessment Health risks HT29 Cells Humans Male MicroRNAs Middle Aged miRNA Nucleotides Occupational Medicine/Industrial Medicine Pharmacology/Toxicology Polymorphism, Single Nucleotide Populations Regression analysis Regulatory sequences Response Elements Risk RNA, Circular - genetics Single-nucleotide polymorphism Smoking Smoking - adverse effects Smoking - genetics Statistical analysis Tumorigenesis |
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Title | Genetic variants in circTUBB interacting with smoking can enhance colorectal cancer risk |
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