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

regional plot of rs60507107 and rs37010.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: regional plot of rs60507107 and rs37010.

Mentions: The replication results are shown in Table 2. Rs60507107 which located in the intron of DAGLA remained to be significantly associated with risk of lung cancer (OR = 1.13, 95%CI = 1.01–1.27, P = 0.037), consistent with the results of the discovery stage (OR = 1.22, 95%CI = 1.12–1.33, P = 4.93 × 10−6). After combining results from two stages, the results demonstrated that rs60507107 was significantly associated with lung cancer (OR = 1.19, 95%CI = 1.11–1.27) at a P-value of 6.98 × 10−7, reaching the significance level after multiple comparison (Bonferroni: 1.54 × 10−6 from 0.05/32,453). The combined ORs for the heterozygote (CT) and minor homozygote (TT) are 1.14 (95%CI = 1.03–1.26) and 1.45 (95%CI = 1.25–1.67), respectively, as compared with major homozygote (CC). The regional plot of rs60507107 was shown in Figure 2. However, the association between the other SNP rs2002059 observed in discovery stage was not replicated 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)

regional plot of rs60507107 and rs37010.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: regional plot of rs60507107 and rs37010.
Mentions: The replication results are shown in Table 2. Rs60507107 which located in the intron of DAGLA remained to be significantly associated with risk of lung cancer (OR = 1.13, 95%CI = 1.01–1.27, P = 0.037), consistent with the results of the discovery stage (OR = 1.22, 95%CI = 1.12–1.33, P = 4.93 × 10−6). After combining results from two stages, the results demonstrated that rs60507107 was significantly associated with lung cancer (OR = 1.19, 95%CI = 1.11–1.27) at a P-value of 6.98 × 10−7, reaching the significance level after multiple comparison (Bonferroni: 1.54 × 10−6 from 0.05/32,453). The combined ORs for the heterozygote (CT) and minor homozygote (TT) are 1.14 (95%CI = 1.03–1.26) and 1.45 (95%CI = 1.25–1.67), respectively, as compared with major homozygote (CC). The regional plot of rs60507107 was shown in Figure 2. However, the association between the other SNP rs2002059 observed in discovery stage was not replicated 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