Correlating blood-based DNA methylation markers and prostate cancer risk factors in African-American men

Background: Detection of prostate cancer at an early stage is key for successful treatment and improvement of outcome. However, the limitations of PSA screening are well recognized and therefore novel approaches to prostate cancer screening are necessary. We have investigated the clinical significance of DNA methylation in the blood serum of African-American men with prostate cancer. Method: We used pyrosequencing to examine the promoter methylation for a panel of 8 genes in blood samples extracted from 91 prostate cancer cases and 91 noncancerous control cases. Results: Seven of the 8-gene panel–RARβ2, TIMP3, SPARC, CDH13, LINE1, CYB5R2 and DRD2–tested achieved significant difference between the cancer cases when compared to control cases. The RARβ2 and TIMP3 demonstrated significant association of DNA methylation with age for all cases analyzed. Associations of methylation status and various clinicopathologic features and patient survival were evaluated: we observed significant inverse association of serum vitamin D levels in the cancer cases and DNA methylation of CDH13 and also an inverse correlation between TIMP3 and DRD2 methylation with supplementary vitamin D in the cancer cases. On the other hand, we observed a direct correlation between HIN1 methylation and serum vitamin D level. In addition, we observed a direct correlation between RARβ2 and Sparc methylation with PSA level in the control but not the cancer cases. Conclusion: Promoter methylation occurred more frequently in the serum of patients with prostate cancer than noncancerous cases, suggesting that epigenetic markers in serum have potential for diagnosis of prostate cancer in AA men. Citation Format: Bernard Kwabi-Addo, Emmauel Moses-Fynn, Wei Tang, Desta Beyene, Victor Apprey, Yasmine Kanaan. Correlating blood-based DNA methylation markers and prostate cancer risk factors in African-American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3327.