MutL homolog (MLH1) is one of several DNA mismatch repair genes of which defects can result in mutation and genomic instability, and ultimately may lead to cancer. Polymorphisms of MLH1 promoter have been shown to be a risk for several types of cancers and thus, we hypothesize that MLH1 promoter polymorphisms can be a risk factor for prostatic diseases. To test this hypothesis, the genetic distribution of MLH1 polymorphism of the promoter region at nucleotide positions prior to translation start site at −1913 (rs34013758), −593 (rs34566456), −93 (rs1800734) and recently identified −107 (base change C to G) were analyzed in 131 normal healthy subjects, 134 benign prostatic hyperplasia (BPH), and 177 sporadic prostate cancer samples in a Japanese population by sequence-specific PCR and sequencing. These experiments show that the variant G/G genotype at the −93 location is associated with prostate cancer when compared to normal controls. Odds ratio and 95% confidence interval for cancer were 1.93 and 1.01-3.69, respectively, for the variant G/G genotype when compared to wildtype (A/A). Likewise, the variant G allele was associated as a risk for prostate cancer (P=0.063). However, no differences were observed for the promoter −93 polymorphism between BPH and controls as well as between stages or grades of prostate cancer. Interestingly, when analyzing the promoter −93 site with the Ile219Val (A to G) polymorphic site, a significant linkage was observed among controls (D’=1). Haplotype analysis showed bases A-A reflecting the wildtype forms for −93 and Ile219Val sites, respectively, to be significantly reduced in cancer compared to controls (P=0.033). The promoter −107 site was extremely rare with C/G type observed in one cancerous patient whereas rs34013758 and rs34566456 were not observed in this Asian population. This is the first report that demonstrates an association for the MLH1 promoter polymorphism with prostate cancer and these results are important in understanding its role in this disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1863.