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The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer.

ABSTRACT: An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that the region harboring this variant is a transcriptional enhancer, that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts with the MYC proto-oncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant.

SUBMITTER: Pomerantz MM

PROVIDER: S-EPMC2763485 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer.

Pomerantz Mark M MM Ahmadiyeh Nasim N Jia Li L Herman Paula P Verzi Michael P MP Doddapaneni Harshavardhan H Beckwith Christine A CA Chan Jennifer A JA Hills Adam A Davis Matt M Yao Keluo K Kehoe Sarah M SM Lenz Heinz-Josef HJ Haiman Christopher A CA Yan Chunli C Henderson Brian E BE Frenkel Baruch B Barretina Jordi J Bass Adam A Tabernero Josep J Baselga José J Regan Meredith M MM Manak J Robert JR Shivdasani Ramesh R Coetzee Gerhard A GA Freedman Matthew L ML

Nature genetics 20090628 8

An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that the region harboring this variant is a transcriptional enhancer, that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2) and that the risk region physically interacts with the MYC proto-oncogene. These data provide strong support for a biological mechanism underlying this non-protein-coding risk variant. ...[more]

PMID: 19561607

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Project description:BackgroundLong noncoding RNA single nucleotide polymorphisms (lncRNA-SNPs) PCAT1 rs710886, PRNCR1 rs1456315 and CCAT2 rs6983267 on 8q24 region present generalizability in the susceptibility to multiple cancers, however, the influence of rs710886, rs1456315 and rs6983267 on lung cancer has not been assessed. The aim of this study was to investigate associations between three lncRNA-SNPs and lung cancer.MethodsA case-control study was performed on 438 patients with lung cancer and 456 healthy controls in the Han population from southern China. The collected samples were genotyped by the TaqMan genotyping, and the association with clinical characteristics, including age, gender, drinking status, smoking status, pathological types and clinical stages were analyzed. And the SNP function prediction was based on lncRNASNP2, RNAfold and GTEx.ResultsThe rs1456315 T allele increased the risk of lung cancer [OR=1.95, 95% CI (1.58-2.43), P=0.003] compared to the rs1456315 C allele, and rs1456315 significantly increased the risk of lung cancer in the dominant model [OR=1.86, 95% CI (1.16-3.00), P=0.002]. The rs6983267 G allele, compared with the T allele, increased the risk of lung cancer [OR=1.29, 95% CI (1.07-1.57), P=0.007], and rs6983267 was identified as a risk factor for lung cancer [OR=1.28, 95% CI (1.06-1.55), P=0.003] in the additive model. Both rs1456315 and rs6983267 demonstrated significance after adjusting for the smoking status, drinking status and age. The structure prediction found rs6983267 and rs1456315 influence the secondary structure of its lncRNA. The results from lncRNASNP2 indicated that rs6983267 and rs1456315 change gain/loss target of miRNAs.ConclusionPRNCR1 rs1456315 and CCAT2 rs6983267 on 8q24 region are significantly associated with lung cancer in the Han population of southern China and alter the potential biological function in bioinformatic analysis, and the results further extended generalism of the susceptibility of cancer-associated lncRNA-SNPs to lung cancer and underlying mechanism involved in lung cancer.

Dataset Information

The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer.

Publications

The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer.

Similar Datasets

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