DNA methylation marks that are inherited from parents to offspring are known to play a role in cancer risk and could explain part of the familial risk for cancer. We therefore conducted a genome-wide search for heritable methylation marks associated with prostate cancer risk. Peripheral blood DNA methylation was measured for 133 of the 469 members of 25 multiple-case prostate cancer families, using the EPIC array. We used these families to systematically search the genome for methylation marks with Mendelian patterns of inheritance, then we tested the 1,000 most heritable marks for association with prostate cancer risk. After correcting for multiple testing, 41 heritable methylation marks were associated with prostate cancer risk. Separate analyses, based on 869 incident cases and 869 controls from a prospective cohort study, showed that 9 of these marks near the metastable epiallele VTRNA2-1 were also nominally associated with aggressive prostate cancer risk in the population.

众所周知，从父母遗传给后代的 DNA 甲基化标记在癌症风险中发挥着重要作用，并且可以部分解释家族性癌症风险。因此，我们对与前列腺癌风险相关的可遗传甲基化标记进行了全基因组搜索。使用 EPIC 阵列对 25 个多病例前列腺癌家族的 469 名成员中的 133 名成员的外周血 DNA 甲基化进行了测量。我们利用这些家族系统地搜索基因组中具有孟德尔遗传模式的甲基化标记，然后测试了 1,000 个最易遗传的标记与前列腺癌风险的关联。经过多次测试校正后，41 个可遗传的甲基化标记与前列腺癌风险相关。基于前瞻性队列研究中的 869 个事件病例和 869 个对照进行的单独分析，