Epigenome-Wide Association Study Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk.
Epigenome-Wide Association Study Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk.
复制标题
DOI：
10.1093/jncics/pkaa041
复制
发表时间：
2020-10
影响因子：
4.4
通讯作者：
Kelsey KT
中科院分区：
文献类型：
--
作者：
Michaud DS;Ruan M;Koestler DC;Pei D;Marsit CJ;De Vivo I;Kelsey KT
使用外周血的全表观基因组关联研究已经确定了与各种癌症风险相关的DNA甲基化的特定位点，并可能有望确定新的风险生物标志物；然而，很少有针对胰腺癌的研究，也没有采用前瞻性研究设计。采用嵌套病例-对照研究设计，从3项前瞻性队列研究中基线提供血液的参与者中确定胰腺癌病例和匹配对照。使用Illumina MethylationEPIC阵列测量从白细胞中提取的DNA的DNA甲基化水平。该分析的平均随访期为13年。在病例和对照组中发现了几个新的基因组区域甲基化差异；其中，位于TMEM204/IFT140、MFSD6L、FAM134B/RETREG1、KCNQ1D和C6orf227基因的CpGs关联最强。对于一些位于16p13.3染色体上的CpGs（靠近TMEM204和IFT140基因），随着诊断时间的缩短，相关性更强（例如，优势比[OR] = 5.95, 95%可信区间[CI] = 1.52至23.12，在抽血与癌症诊断之间<5年，上四分位数vs下四分位数），但即使在抽血后10年以上诊断出病例，相关性仍然具有统计学意义上的显著性。通过基因集富集分析（GSEA）分析，还观察到胃液分泌途径中DNA甲基化水平的差异具有统计学意义。外周血中DNA甲基化的变化可能标志着在胰腺癌中起作用的代谢或免疫途径的改变。利用全表观基因组关联研究方法识别胰腺癌癌变的新生物学途径，可以为改善治疗和预防提供新的机会。
Epigenome-wide association studies using peripheral blood have identified specific sites of DNA methylation associated with risk of various cancers and may hold promise to identify novel biomarkers of risk; however, few studies have been performed for pancreatic cancer and none using a prospective study design. Using a nested case-control study design, incident pancreatic cancer cases and matched controls were identified from participants who provided blood at baseline in 3 prospective cohort studies. DNA methylation levels were measured in DNA extracted from leukocytes using the Illumina MethylationEPIC array. Average follow-up period for this analysis was 13 years. Several new genomic regions were identified as being differentially methylated in cases and controls; the 5 strongest associations were observed for CpGs located in genes TMEM204/IFT140, MFSD6L, FAM134B/RETREG1, KCNQ1D, and C6orf227. For some CpGs located in chromosome 16p13.3 (near genes TMEM204 and IFT140), associations were stronger with shorter time to diagnosis (eg, odds ratio [OR] = 5.95, 95% confidence interval [CI] = 1.52 to 23.12, for top vs bottom quartile, for <5 years between blood draw and cancer diagnosis), but associations remained statistically significantly higher even when cases were diagnosed over 10 years after blood collection. Statistically significant differences in DNA methylation levels were also observed in the gastric secretion pathway using Gene Set Enrichment Analysis (GSEA) analysis. Changes in DNA methylation in peripheral blood may mark alterations in metabolic or immune pathways that play a role in pancreatic cancer. Identifying new biological pathways in carcinogenesis of pancreatic cancer using epigenome-wide association studies approach could provide new opportunities for improving treatment and prevention.
登录
查看更多内容
从头开始鉴定人基因组中差异甲基化区域。
影响因子：
3.9
作者：
Peters TJ;Buckley MJ;Statham AL;Pidsley R;Samaras K;V Lord R;Clark SJ;Molloy PL
通讯作者：
Molloy PL
影响因子：
6.2
作者：
Liggett, Thomas;Melnikov, Anatoliy;Levenson, Victor
通讯作者：
Levenson, Victor
影响因子：
3.7
作者：
Islam, Farhadul;Gopalan, Vinod;Lam, Alfred King-yin
通讯作者：
Lam, Alfred King-yin
影响因子：
11.1
作者：
Bartlett, Alexandra H.;Liang, Jane W.;Mozhui, Khyobeni
通讯作者：
Mozhui, Khyobeni
白细胞 DNA 甲基化特征可将胰腺癌患者与健康对照区分开来。
影响因子：
3.7
作者：
Pedersen KS;Bamlet WR;Oberg AL;de Andrade M;Matsumoto ME;Tang H;Thibodeau SN;Petersen GM;Wang L
通讯作者：
Wang L