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Functional variants of -1318T > G and -673C > T in c-Jun promoter region associated with increased colorectal cancer risk by elevating promoter activity
- Source :
- Carcinogenesis. 32:1043-1049
- Publication Year :
- 2011
- Publisher :
- Oxford University Press (OUP), 2011.
-
Abstract
- 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, -673CT and rs2760501, -1318TG) 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 (P0.05 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 -673CT and -1318TG 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.
- Subjects :
- Male
Cancer Research
Genotype
Proto-Oncogene Proteins c-jun
medicine.disease_cause
Polymorphism, Single Nucleotide
Humans
Medicine
Genetic Predisposition to Disease
Genetic variability
Promoter Regions, Genetic
Genetic association
Genetics
business.industry
Haplotype
Cancer
Promoter
General Medicine
Odds ratio
Middle Aged
medicine.disease
Mutation
Cancer research
Female
Colorectal Neoplasms
business
Carcinogenesis
Plasmids
Subjects
Details
- ISSN :
- 14602180 and 01433334
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....97d338f197ed42735f7a73c8cdf38845