Journal Article

Functional variants of -1318T > G and -673C > T in <i>c-Jun</i> promoter region associated with increased colorectal cancer risk by elevating promoter activity

Dianke Chen, Shunxin Song, Jiachun Lu, Yanxin Luo, Zuli Yang, Qinghua Huang, Xinhui Fu, Xinjuan Fan, Yisheng Wei, Jianping Wang and Lei Wang

in Carcinogenesis

Volume 32, issue 7, pages 1043-1049
Published in print July 2011 | ISSN: 0143-3334
Published online March 2011 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgr047
Functional variants of -1318T > G and -673C > T in c-Jun promoter region associated with increased colorectal cancer risk by elevating promoter activity

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C-Jun plays important roles in the development of multiple cancers, but no well-designed association studies have been conducted to assess the roles of its genetic polymorphisms in cancer risk. In a cohort of 1016 pairs of colorectal cancer (CRC) patients and matched cancer-free controls, we investigated two genetic polymorphisms in the promoter regions of the c-Jun (rs4646999, -673C > T and rs2760501, -1318T > G) via the Taqman assay and evaluated the association between two polymorphisms and risk of CRC. We found that both the -1318G and -673C variant genotypes were associated with an increased risk of CRC [-1318TG: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.04–1.54; −1318GG: OR = 1.63, 95% CI = 1.03–2.60; -673CT: OR = 1.60, 95% CI = 1.23–2.07; -673CC: OR = 1.80, 95% CI = 1.36–2.37]. Haplotype association analysis showed that compared with the carriers of -1318T-673T haplotype, carriers of the -1318T-673C, -1318G-673T, and -1318G-673C haplotypes all had a significantly increased risk of CRC (P < 0.05 for all). The combined genotypes incorporating both polymorphisms obtained a more significantly additive risk of CRC (one variant genotype: OR = 1.81, 95% CI = 1.30–2.51; two variant genotype: OR = 2.42, 95% CI = 1.70–3.44). Moreover, we found that the change of the -1318T to G allele interact with the -673T to C allele elevated the transcription activity of the c-Jun, and we confirmed the same trends by analyzing c-Jun protein expression in the CRC tissues from patients carrying different number of variant genotypes. This study suggests that -673C > T and -1318T > G genetic variants in c-Jun promoter regions contribute to an increased risk of CRC, possibly by elevating the transcription activity and protein expression levels that appeared to upregulate activity of c-Jun thus tumorigenesis.

Journal Article.  6497 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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