Dysregulation of DNA Methylation and Epigenetic Clocks in Prostate Cancer among Puerto Rican Men.

Jong Y. Park ,Young‐Chul Kim ,Carmen Ortiz-Sanchéz ,Julie Dutil,Anders Berglund,Natasha Moreno ,Kosj Yamoah,Jasreman Dhillon,Ratna Chakrabarti,Raymond Linares,Hui‐Yi Lin ,Liang Wang,Ryan M. Putney ,Carlos J. Díaz Osterman ,Joshua Marcial,Gilberto Ruiz-Deya,Seung Joon Kim ,Jarline Encarnación-Medina ,Caren Abreu-Takemura,Jaime Matta

doi:10.3390/biom12010002

Abstract

In 2021, approximately 248,530 new prostate cancer (PCa) cases are estimated in the United States. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. The objective of this study was to assess DNA methylation patterns between aggressive and indolent PCa along with ancestry proportions in 49 H/L men from Puerto Rico (PR). Prostate tumors were classified as aggressive (n = 17) and indolent (n = 32) based on the Gleason score. Genomic DNA samples were extracted by macro-dissection. DNA methylation patterns were assessed using the Illumina EPIC DNA methylation platform. We used ADMIXTURE to estimate global ancestry proportions. We identified 892 differentially methylated genes in prostate tumor tissues as compared with normal tissues. Based on an epigenetic clock model, we observed that the total number of stem cell divisions (TNSC) and stem cell division rate (SCDR) were significantly higher in tumor than adjacent normal tissues. Regarding PCa aggressiveness, 141 differentially methylated genes were identified. Ancestry proportions of PR men were estimated as African, European, and Indigenous American; these were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation profiles associated with risk and aggressiveness of PCa in PR H/L men will shed light on potential mechanisms contributing to PCa disparities in PR population.

Highlights

Based on American Cancer Society data, 248,530 new prostate cancer (PCa) cases and34,130 PCa-specific deaths are anticipated in the US in 2021 [1]
We recently reported differentially methylated genes in PCa tumor tissues and methylated genes associated with aggressiveness in a small number of Puerto Rico (PR) men with PCa [26]
Puerto Rican Hispanic/Latino men are at an increased risk of prostate cancer-specific mortality compared with non-Hispanic Whites (NHWs) men

Summary

Introduction

Based on American Cancer Society data, 248,530 new prostate cancer (PCa) cases and34,130 PCa-specific deaths are anticipated in the US in 2021 [1]. The lifetime risk of PCa is Biomolecules 2022, 12, 2. PCa-specific mortality (PCSM) rates have been found to vary among different ethnic groups in the US. The study by Chinea et al (2017) reported differences in PCSM rates when comparing Hispanic/Latino (H/L) subgroups to non-Hispanic Whites (NHWs) and non-Hispanic Blacks (NHBs) [3]. This study aggregated all H/L subgroups into one broad group including: Mexican Americans, Puerto Ricans, Cubans, South or Central Americans, and Dominicans. Among different H/L subgroups, Puerto Rican (PR) men showed much higher PCSM rates than other Hispanic groups and NHBs [3]. In Puerto Rico (PR), PCa is the most common type of cancer case and accounts for the most cancer-specific deaths [4]

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