Alkylating agents such as temozolomide (TMZ) are effective anticancer drugs for treating a variety of solid tumors including melanoma, glioma, and astrocytoma. TMZ exerts its effects mainly via the mutagenic product O(6)-methylguanine, a cytotoxic DNA lesion. This damage may be repaired by the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT), a key player in the resistance of cancers to TMZ. Several strategies are presently being pursued to improve the killing of tumor cells by TMZ, with inhibition of MGMT being the most promising. In this review, we provide an overview of recent advances in this field.

ABSTRACT. Recent evidence suggests that genetic variations in the IGFBP-3 gene may impact susceptibility to colorectal cancer, but individually published results are inconclusive. Our meta-analysis was aimed at providing a more precise estimation of these associations. An extensive literature search was conducted for appropriate articles published before May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eleven case-control studies were included with a total of 11,895 colorectal cancer patients and 17,147 healthy controls. Our meta-analysis indicated that the G variant of IGFBP-3 C2133G polymorphism may be associated with increased colorectal cancer risk. However, no statistically significant association was noted between IGFBP-3 A-202C polymorphism and colorectal cancer risk. No publication bias was detected in this metaanalysis. The current meta-analysis suggests that the IGFBP-3 C2133G polymorphism may confer susceptibility to colorectal cancer. The G IGFBP-3 A-202C and C2133G in colorectal cancer risk variant of the IGFBP-3 C2133G polymorphism may serve as a useful biomarker for predicting the risk of colorectal cancer.