Abstract
Global DNA methylation of long interspersed nucleotide elements (LINE-1) in leukocytes has been suggested to be a risk factor for a few cancers. There has been no report of LINE-1 methylation in leukocytes as a risk factor for aggressive prostate cancer at diagnosis and prognosis after treatments. In this study, we measured the leukocyte DNA methylation of LINE-1 in 795 PCa patients and compared the methylation levels across different clinical subgroups. We then determined the association of LINE-1 methylation in leukocytes with clinicopathological variables at diagnosis using logistic regression analysis and biochemical recurrence in patients receiving active treatments (prostatectomy and radiotherapy) using Cox proportional hazard model after adjusting for age, BMI, smoking status, pack year, D’Amico risk groups, and treatments. Overall, the DNA methylation of LINE-1 was not associated with the risk of being diagnosed with high-risk prostate cancer or the risk of biochemical recurrence upon active treatments. Future studies are warranted to investigate other types of repetitive element methylation and longitudinal changes of global methylation in relation to prostate cancer risk and prognosis.
Highlights
Prostate cancer (PCa) represents the most common cancer and the third leading cause of cancer death in American men [1]
Methylation profile is an inheritable feature that could affect genomic instability and gene expression. This is the first study to evaluate the association of LINE-1 DNA methylation in peripheral blood leukocytes with the aggressiveness of prostate cancer
The three sites we measured represent hundreds of thousands of same sequences in the genome, which is the reason that the methylation analysis of a short LINE1 sequence can be used as an indicator of global DNA methylation
Summary
Prostate cancer (PCa) represents the most common cancer and the third leading cause of cancer death in American men [1]. The prognosis of PCa, for locoregional PCa, has been excellent with a 5-year survival rate of 99%, overdiagnosis and overtreatment has become a rising clinical issue for PCa due to the limited ability of PSA screening to differentiate aggressive from indolent diseases [2]. Other clinical variables, such as tumor stage and Gleason Score (GS), are not able to accurately distinguish aggressive and indolent PCa at diagnosis. No study has evaluated the role of global leukocyte DNA methylation in the prognosis of localized PCa patients
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