Limits...
Systematical analyses of variants in CTCF-binding sites identified a novel lung cancer susceptibility locus among Chinese population.

Dai J, Zhu M, Wang C, Shen W, Zhou W, Sun J, Liu J, Jin G, Ma H, Hu Z, Lin D, Shen H - Sci Rep (2015)

Bottom Line: Genome-wide association studies identified genetic susceptibility variants mostly lie outside of protein-coding regions.A two-stage case-control design was conducted to evaluate the variants located at the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs 1,346).Imputation was performed to increase the genome coverage in the CTCF binding regions.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Genome-wide association studies identified genetic susceptibility variants mostly lie outside of protein-coding regions. It suggested variants located at transcriptional regulatory region should play an important role in cancer carcinogenesis including lung cancer. In the present study, we systematically investigated the associations between the variants in the binding sites of an extensive transcription factor CTCF and lung cancer risk in Chinese population. A two-stage case-control design was conducted to evaluate the variants located at the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs 1,346). The ChIP-seq data for CTCF, specified on lung cancer cell line A549, were downloaded from ENCODE database. Imputation was performed to increase the genome coverage in the CTCF binding regions. Three variants in CTCF binding sites were found to associate with lung cancer risk in the first stage. Further replication revealed a novel single nucleotide polymorphism rs60507107 was significantly associated with increased risk of lung cancer in two stages (Additive model: OR = 1.19, 95%CI = 1.11-1.27, P = 6.98 × 10(-7)). Our results indicate that rs60507107 in the binding site of CTCF is associated with an increased risk of lung cancer. This may further advance our understanding of regulatory DNA sequences in cancer development.

No MeSH data available.


Related in: MedlinePlus

rs60507107 in CTCF TFBS Chip-seq peaks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4296290&req=5

f1: rs60507107 in CTCF TFBS Chip-seq peaks.

Mentions: A total of 2,331 cases and 3,077 controls were included in the discovery stage, 1,115 cases and 1,346 controls in the validation stage. The demographic and clinical information is summarized in Supplementary Table 2. Before imputation, only 3,569 genotyped SNPs in the CTCF binding peaks exited in our GWAS data set. After imputation, the data coverage increased more than eight fold, a total of 32,453 qualified SNPs in the binding sites were analyzed in the discovery stage and three SNPs (rs37010 in 5p15.33, rs2002059 in 10q24.2, rs60507107 in 11q12.2 ) met all the criteria above (Table 1, Figure 1 and Supplementary figure 2–3). However, rs37010 was in strong LD with rs465498 (R2 = 0.94) which had been confirmed related to lung cancer risk in our previous study16, so it was no longer validated in this study. As a result, two SNPs (rs2002059 and rs60507107) were further evaluated in the validation stage.


Systematical analyses of variants in CTCF-binding sites identified a novel lung cancer susceptibility locus among Chinese population.

Dai J, Zhu M, Wang C, Shen W, Zhou W, Sun J, Liu J, Jin G, Ma H, Hu Z, Lin D, Shen H - Sci Rep (2015)

rs60507107 in CTCF TFBS Chip-seq peaks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296290&req=5

f1: rs60507107 in CTCF TFBS Chip-seq peaks.
Mentions: A total of 2,331 cases and 3,077 controls were included in the discovery stage, 1,115 cases and 1,346 controls in the validation stage. The demographic and clinical information is summarized in Supplementary Table 2. Before imputation, only 3,569 genotyped SNPs in the CTCF binding peaks exited in our GWAS data set. After imputation, the data coverage increased more than eight fold, a total of 32,453 qualified SNPs in the binding sites were analyzed in the discovery stage and three SNPs (rs37010 in 5p15.33, rs2002059 in 10q24.2, rs60507107 in 11q12.2 ) met all the criteria above (Table 1, Figure 1 and Supplementary figure 2–3). However, rs37010 was in strong LD with rs465498 (R2 = 0.94) which had been confirmed related to lung cancer risk in our previous study16, so it was no longer validated in this study. As a result, two SNPs (rs2002059 and rs60507107) were further evaluated in the validation stage.

Bottom Line: Genome-wide association studies identified genetic susceptibility variants mostly lie outside of protein-coding regions.A two-stage case-control design was conducted to evaluate the variants located at the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs 1,346).Imputation was performed to increase the genome coverage in the CTCF binding regions.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Epidemiology and Biostatistics and Ministry of Education (MOE), Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2] Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Genome-wide association studies identified genetic susceptibility variants mostly lie outside of protein-coding regions. It suggested variants located at transcriptional regulatory region should play an important role in cancer carcinogenesis including lung cancer. In the present study, we systematically investigated the associations between the variants in the binding sites of an extensive transcription factor CTCF and lung cancer risk in Chinese population. A two-stage case-control design was conducted to evaluate the variants located at the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs 1,346). The ChIP-seq data for CTCF, specified on lung cancer cell line A549, were downloaded from ENCODE database. Imputation was performed to increase the genome coverage in the CTCF binding regions. Three variants in CTCF binding sites were found to associate with lung cancer risk in the first stage. Further replication revealed a novel single nucleotide polymorphism rs60507107 was significantly associated with increased risk of lung cancer in two stages (Additive model: OR = 1.19, 95%CI = 1.11-1.27, P = 6.98 × 10(-7)). Our results indicate that rs60507107 in the binding site of CTCF is associated with an increased risk of lung cancer. This may further advance our understanding of regulatory DNA sequences in cancer development.

No MeSH data available.


Related in: MedlinePlus