Abstract 86: Functional effects of MutL homolog 1 promoter polymorphism in prostate cancer

The mutL homolog (MLH1) gene protects the integrity of the genome by correcting erroneous insertions, deletions and mismatches that occur during DNA replication. Proper MLH1 expression is thus essential for the health of the cell and deficiency can result in mutation and genomic instability, which ultimately may lead to cancer. Polymorphisms in the promoter region can lead to altered gene expression and we tested the hypothesis that MLH1 promoter variants can affect levels as well as be a risk for prostatic cancer. Two polymorphic sites were analyzed, rs1800734 (A to G) and rs4647203 (G to A). A luciferase reporter construct containing the MLH1 promoter region was utilized and site-directed mutagenesis was performed to create rs1800734 and rs4647203 variants. Activity was tested using DU145, PC3 and LNCaP prostatic cells and interestingly, the rs1800734 G variant resulted in significantly decreased luciferase levels in all three cell lines compared to A (P Citation Format: Shinichiro Fukuhara, Yozo Mitsui, Yutaka Hashimoto, Taku Kato, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Functional effects of MutL homolog 1 promoter polymorphism in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 86.