Promoter methylation of PGC1A and PGC1B predicts cancer incidence in a veteran cohort

Abstract

<div class="section"> <a class="named-anchor" id="d1038020e364"> <!-- named anchor --> </a> <h5 class="section-title" id="d1038020e365">Aim:</h5> <p id="d1038020e367">Previous studies suggest telomere shortening represses <i>PGC1A</i> and <i>PGC1B</i> expression leading to mitochondrial dysfunction. Methylation of CpG sites within these genes may interact with these factors to affect cancer risk. </p> </div><div class="section"> <a class="named-anchor" id="d1038020e375"> <!-- named anchor --> </a> <h5 class="section-title" id="d1038020e376">Materials &amp; methods:</h5> <p id="d1038020e378">Among 385 men, we identified 84 incidents of cancers (predominantly prostate and nonmelanoma skin). We examined associations between leukocyte DNA methylation of 41 CpGs from <i>PGC1A</i> and <i>PGC1B</i> with telomere length, mitochondrial 8-OHdG lesions, mitochondrial abundance and cancer incidence. </p> </div><div class="section"> <a class="named-anchor" id="d1038020e386"> <!-- named anchor --> </a> <h5 class="section-title" id="d1038020e387">Results:</h5> <p id="d1038020e389">Methylation of five and eight CpG sites were significantly associated with telomere length and mitochondrial abundance at p &lt; 0.05. Two CpG sites were independently associated with cancer risk: cg27514608 ( <i>PGC1A</i>, TSS1500; HR: 1.55, 95% CI: 1.19–2.03, FDR = 0.02), and cg15219393 ( <i>PGC1B</i>, first exon/5′UTR; HR: 3.71, 95% CI: 1.82–7.58, FDR &lt; 0.01). Associations with cg15219393 were observed primarily among men with shorter leukocyte telomeres. </p> </div><div class="section"> <a class="named-anchor" id="d1038020e397"> <!-- named anchor --> </a> <h5 class="section-title" id="d1038020e398">Conclusion:</h5> <p id="d1038020e400"> <i>PGC1A</i> and <i>PGC1B</i> methylation may serve as early biomarkers of cancer risk. </p> </div>