与乳腺癌和前列腺癌风险相关的可遗传甲基化标记。

Heritable methylation marks associated with breast and prostate cancer risk.

作者信息

Dugué Pierre-Antoine, Dowty James G, Joo Jihoon E, Wong Ee M, Makalic Enes, Schmidt Daniel F, English Dallas R, Hopper John L, Pedersen John, Severi Gianluca, MacInnis Robert J, Milne Roger L, Giles Graham G, Southey Melissa C

机构信息

Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Victoria, Australia.

Centre for Epidmiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.

出版信息

Prostate. 2018 Sep;78(13):962-969. doi: 10.1002/pros.23654. Epub 2018 May 29.

DOI:10.1002/pros.23654

PMID:30133758

Abstract

BACKGROUND

DNA methylation can mimic the effects of germline mutations in cancer predisposition genes. Recently, we identified twenty-four heritable methylation marks associated with breast cancer risk. As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer.

METHODS

We studied 869 incident prostate cancers (430 aggressive and 439 non-aggressive) and 869 matched controls nested within a prospective cohort study. DNA methylation was measured in pre-diagnostic blood samples using the Illumina Infinium HM450K BeadChip. Conditional logistic regression models, adjusted for prostate cancer risk factors and blood cell composition, were used to estimate odds ratios and 95% confidence intervals for the association between the 24 methylation marks and the risk of prostate cancer.

RESULTS

Five methylation marks within the VTRNA2-1 promoter region (cg06536614, cg00124993, cg26328633, cg25340688, and cg26896946), and one in the body of CLGN (cg22901919) were associated with the risk of prostate cancer. In stratified analyses, the five VTRNA2-1 marks were associated with the risk of aggressive prostate cancer.

CONCLUSIONS

This work highlights a potentially important new area of investigation for prostate cancer susceptibility and adds to our knowledge about shared risk factors for breast and prostate cancer.

摘要

背景

DNA甲基化可模拟癌症易感基因中种系突变的作用。最近，我们鉴定出24个与乳腺癌风险相关的可遗传甲基化标记。由于乳腺癌和前列腺癌具有共同的遗传风险因素，包括罕见的高风险突变（例如BRCA2中的突变），我们推测其中一些可遗传甲基化标记可能也与前列腺癌风险相关。

方法

我们在一项前瞻性队列研究中，对869例新发前列腺癌患者（430例侵袭性和439例非侵袭性）以及869例匹配对照进行了研究。使用Illumina Infinium HM450K BeadChip对诊断前血液样本中的DNA甲基化进行检测。采用经前列腺癌风险因素和血细胞组成调整的条件逻辑回归模型，估计24个甲基化标记与前列腺癌风险之间关联的比值比和95%置信区间。

结果

VTRNA2-1启动子区域内的5个甲基化标记（cg06536614、cg00124993、cg26328633、cg25340688和cg26896946）以及CLGN基因体中的1个甲基化标记（cg22901919）与前列腺癌风险相关。在分层分析中，VTRNA2-1的5个标记与侵袭性前列腺癌风险相关。