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The association between −1304T>G polymorphism in the promoter ofMKK4gene and the risk of sporadic colorectal cancer in southern Chinese population
- Source :
- International Journal of Cancer. 125:1876-1883
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- MKK4 (mitogen-activated protein kinase kinase 4, NM_003010.2), which belongs to the mitogen-activated protein kinase pathways, possesses functions in tumorigenesis. We hypothesized the genetic variants in MKK4 gene may alter its functions and thus cancer risk. In current hospital-based case-control study of 706 patients with sporadic colorectal cancer (CRC) and 723 sex-age–frequency-matched control subjects in a southern Chinese population, we genotyped two polymorphisms of MKK4 promoter (i.e., −1304T>G, rs3826392 and −1044A>T, rs3809728) and assessed their associations with the risk of sporadic CRC. Compared with −1304TT genotypes, −1304TG had a significantly decreased risk of CRC (adjusted odds ratios [OR] = 0.56; 95% CI = 0.44–0.72; p = 3.53 × 10−6), the −1304GG carriers had a further decreased risk of CRC (OR = 0.40; 95% CI = 0.23–0.70; p = 1.32 × 10−3), and there was a significant trend for an allele dose effect on risk of CRC (ptrend = 2.64 × 10−7). The decreased risk associated with −1304G variant genotypes (i.e., TG+GG) was more pronounced in the subjects older than 60 years (adjusted OR = 0.41; 95% CI = 0.29–0.57; p = 2.25 × 10−7), in ever drinkers (adjusted OR = 0.41; 95% CI = 0.28–0.59; p = 2.42 × 10−6). The age and alcohol drinking status interacted with −1304G variant genotypes on reducing cancer risk (p values for interaction were 0.015 and 0.043, respectively). Western blotting analysis showed that the levels of Mkk4 protein in sporadic CRC neoplastic tissues were significantly higher in the carriers of −1304G variant genotypes than that in those with −1304TT genotypes. However, no significant association was observed between −1044A>T polymorphism and risk of CRC. To the best of our knowledge, this is the first study of genetic variants in MKK4 and cancer susceptibility. Larger studies are needed to validate our findings. © 2009 UICC
- Subjects :
- Male
Oncology
China
Cancer Research
medicine.medical_specialty
Genotype
MAP Kinase Kinase 4
Colorectal cancer
Blotting, Western
Population
Single-nucleotide polymorphism
Biology
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Asian People
Risk Factors
Internal medicine
medicine
Humans
Genetic variability
Allele
Promoter Regions, Genetic
education
education.field_of_study
Cancer
Odds ratio
Middle Aged
medicine.disease
Case-Control Studies
Immunology
Female
Colorectal Neoplasms
Subjects
Details
- ISSN :
- 10970215 and 00207136
- Volume :
- 125
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi.dedup.....90ce47942c5f4321a9c8ac6e73a58241