海报库PosterKeep
PO.PS01.07 · 人群科学

外周血中MYC外显子3的DNA甲基化与前列腺、肺、结直肠和卵巢癌筛查试验中侵袭性前列腺癌的风险

MYC exon 3 DNA methylation in peripheral blood and the risk of aggressive prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

编号 3599 展板 17 时间 4/20 02:00–05:00 区域 Section 35 主讲 Kathryn Barry, MPH;PhD
分会场 Genetic Epidemiology 1: GxE, GWAS, Polygenic Risk Scores, and Post-GWAS
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作者与单位 Authors & Affiliations

Patricia A. Erickson1, Lauren M. Hurwitz2, Søren M. Bentzen3, Stella Koutros2, Liying Yan4, Matthew L. Poulin4, Ann Meyer4, Allen Burke3, Arif Hussain3, Sonja I. Berndt2, Kathryn Hughes Barry3

1Huntsman Cancer Institute, Salt Lake City, UT,2National Cancer Institute, Rockville, MD,3University of Maryland School of Medicine, Baltimore, MD,4EpigenDx, Inc., Hopkinton, MA

摘要 Abstract

中文摘要
引言：我们团队此前报道，外周血中MYC外显子3两个CpG位点较高的DNA甲基化与侵袭性前列腺癌风险升高相关（Barry等，Br J Cancer 2017）。在此，我们旨在评估针对这些CpG位点的发现是否能在一组独立的男性中得到重复验证。 方法：使用诊断前血样，我们在前列腺、肺、结直肠和卵巢（PLCO）癌症筛查试验中未纳入我们此前PLCO研究的非西班牙裔白人男性中开展了一项巢式前列腺癌病例对照研究。病例包括251名确诊为新发侵袭性前列腺癌（III期或IV期或Gleason总评分≥8）的男性，对照包括497名既往无前列腺癌病史的男性。对照与病例按若干因素进行个体匹配，包括采血时年龄（±3年）、采血日历年份（±3年）、采血研究年份、样本类型（即全血或白膜层）以及DNA来源（即来自PLCO既往基因分型工作的现有DNA或新提取的DNA）。使用焦磷酸测序在经亚硫酸氢盐处理的DNA上定量MYC外显子3区域内目标CpG位点的DNA甲基化百分比，这些位点标记为CpG 214（GRCh37/hg19坐标：Chr8:128753154）和CpG 215（Chr8:128753187）。我们使用条件logistic回归估计DNA甲基化水平（作为连续变量建模）与侵袭性前列腺癌相关的比值比（OR）和95%置信区间（95%CI）。我们还进行了荟萃分析以合并两项研究的结果（共423例侵袭性前列腺癌病例）。 结果：对于CpG 214和215，我们观察到DNA甲基化每增加一个单位，侵袭性前列腺癌风险升高（CpG 214：OR=1.05，95%CI：0.99-1.12；CpG 215：OR=1.03，95%CI：0.97-1.09）。将这些结果与我们此前研究进行荟萃分析时，我们在两个CpG位点均观察到类似且具统计学显著性的模式（CpG 214：OR=1.06，95%CI：1.02-1.10；CpG 215：OR=1.05，95%CI：1.01-1.10）。 结论：这些发现丰富了关于MYC在前列腺癌发生中作用的文献，支持外周血中MYC外显子3较高的诊断前DNA甲基化水平与非西班牙裔白人男性侵袭性前列腺癌风险升高相关。需要在更多样化的人群中开展进一步研究。
查看英文原文 English abstract
Introduction : Our group previously reported that higher DNA methylation at two CpG sites in MYC exon 3 in peripheral blood was associated with a higher risk of aggressive prostate cancer (Barry et al, Br J Cancer 2017). Here we aimed to assess if our findings for these CpG sites would replicate in an independent group of men. Methods : Using pre-diagnostic blood samples, we conducted a nested prostate cancer case-control study among non-Hispanic White men in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial who were not included in our previous study in PLCO. Cases comprised 251 men who were diagnosed with incident aggressive prostate cancer (stage III or IV or a total Gleason score>=8), and controls comprised 497 men without a previous history of prostate cancer. The controls were individually matched to the cases on several factors, including age at blood draw (+/- 3 yrs), calendar year of blood draw (+/- 3 years), study year of blood draw, sample type (i.e., whole blood or buffy coat), and the source of the DNA (i.e., available DNA from previous genotyping efforts in PLCO or new extractions). Percent DNA methylation at the CpG sites of interest in the exon 3 region of MYC , denoted as CpG 214 (GRCh37/hg19 coordinate: Chr8:128753154) and CpG 215 (Chr8:128753187), was quantified using pyrosequencing on bisulfite-treated DNA. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for DNA methylation levels, modeled as a continuous variable, in relation to aggressive prostate cancer. We also conducted a meta-analysis to combine the results from our two studies (total of 423 aggressive prostate cancer cases). Results : For both CpG 214 and 215, we observed an elevated risk of aggressive prostate cancer with each unit increase of DNA methylation (for CpG 214, OR=1.05, 95% CI: 0.99-1.12, and for CpG 215, OR=1.03, 95% CI: 0.97-1.09). We observed similar patterns that were statistically significant for both CpG sites when meta-analyzing these results with our previous study (for CpG 214, OR=1.06, 95% CI: 1.02-1.10, and for CpG 215, OR=1.05, 95% CI: 1.01-1.10). Conclusions: Adding to the literature on the role of MYC in prostate carcinogenesis, findings support that higher pre-diagnostic DNA methylation levels in MYC exon 3 in peripheral blood are associated with a higher risk of aggressive prostate cancer among non-Hispanic White men. Further study is needed in more diverse populations.
利益披露 Disclosure
P. A. Erickson, None.. L. M. Hurwitz, None.. S. M. Bentzen, None.. S. Koutros, None. L. Yan, EpigenDx, Inc. Employment, g., Board of Directors, non-salaried role), Stock. M. L. Poulin, EpigenDx, Inc. Employment, Stock. A. Meyer, EpigenDx, Inc. Employment, Stock. A. Burke, None. A. Hussain, Constellation Pharmaceuticals, Inc. ). FORMA Therapeutics ). AstraZeneca ). PSI Pharma Support America, Inc. ). Taiho Oncology Inc. ). Orion Corporation ). Regeneron Pharmaceuticals, Inc. ). Pfizer Incorporated ). Poseida Therapeutics, Inc. ). Exelixis, Inc. ). Aravive Inc. ). Bayer Corporation USA ). Future Chem Co Ltd ). Merck Sharp & Dohme LLC ). Advancing Cancer Treatment ). Nimbus Saturn ). ORIC Pharmaceuticals, Inc. ). S. I. Berndt, None.. K. H. Barry, None.

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