Functional promoter rs2295080 T>G variant in MTOR gene is associated with risk of colorectal cancer in a Chinese population.

BACKGROUND

The mammalian target of rapamycin (mTOR) plays an important role in the development and progression of colorectal cancer (CRC). Recently, a functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to influence its expression and confer susceptibility to cancer. Therefore, in the present study, we sought to investigate the influence of this polymorphism on the risk of CRC.

METHODS

We genotyped this polymorphism by using the TaqMan method in a case-control study comprising of 737 CRC patients and 777 controls. The logistic regression was used to assess the genetic association with occurrence of CRC. The functionality of the polymorphism was examined by luciferase reporter assay.

RESULTS

We found the variant genotypes of MTOR rs2295080 (TG/GG) were significantly associated with decreased CRC risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.76, 95% confidence interval (CI)=0.62-0.94, P=0.011], and the protective effect of this polymorphism was more predominant among the subgroups of elder (OR=0.66, 95% CI=0.49-0.89) and male (OR=0.63, 95% CI=0.48-0.84) subjects. Furthermore, the luciferase reporter assay showed that the rs2295080G allele significantly decreased the luciferase activity in both sw480 and sw620 cell lines (P=0.002 and P<0.001, respectively).

CONCLUSIONS

Our results suggest that the functional rs2295080 T>G in the promoter of MTOR may influence the susceptibility of CRC in the Chinese population through regulating the transcription activity of MTOR promoter. Large population-based prospective studies are required to validate our findings.