Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case-Control Study.
Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case-Control Study.
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DOI：
10.1158/1078-0432.ccr-15-0977
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发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Wu X
中科院分区：
文献类型：
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作者：
Mendoza-Pérez J;Gu J;Herrera LA;Tannir NM;Matin SF;Karam JA;Huang M;Chang DW;Wood CG;Wu X
基因组DNA低甲基化是大多数癌症基因组的标志，促进基因组不稳定性和细胞转化。在本研究中，我们试图确定外周血中的整体DNA甲基化是否与肾细胞癌（RCC）的风险相关。采用回顾性病例对照研究，包括889例RCC病例和相同数量的年龄、性别和种族匹配的对照。总体DNA甲基化测量为5-mC%含量。Logistic回归分析DNA甲基化水平与肾细胞癌发病风险的比值比（OR）和95%可信区间（CI）。病例组的中位数5-mC%显著低于健康对照组（p<0.001）。在多因素Logistic回归分析中，与最高三分位数（T3）的个体相比，最低三分位数（T1）为5-mC%的个体患RCC的风险更高，OR为1.40（95%CI 1.06-1.84）（趋势P =0.02）。当按肾细胞癌危险因素分层时，低甲基化与肾细胞癌风险增加之间的关联似乎在男性中更强（OR=1.61，Pfor trend=0.01），年轻化（OR=1.47，P =0.03），从不吸烟者（OR=1.55，Pfor trend=0.02）、其他癌症家族史（OR=1.64，Pfor trend=1.22E-03）和晚期癌症（OR=2.06，Pfor trend=4.98E-04）。此外，我们观察到性别和5-mC%之间在增加RCC风险方面存在显著的交互作用（交互作用P =0.03）。我们的研究结果表明，全球DNA低甲基化和肾细胞癌风险之间的关联。为了建立全球DNA低甲基化作为RCC的危险因素，未来的前瞻性研究是必要的。本研究为进一步认识肾细胞癌的发病机制提供了依据。
Genomic DNA hypomethylation is a hallmark of most cancer genomes, promoting genomic instability and cell transformation. In the present study, we sought to determine whether global DNA methylation in peripheral blood is associated with risk of renal cell carcinoma (RCC). A retrospective case control study consisting of 889 RCC cases and an equal number of age, gender, and ethnicity-matched controls was applied. Global DNA methylation was measured as 5-mC% content. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between DNA methylation level and the risk of RCC. The median 5-mC% was significantly lower in cases than healthy controls (p<0.001). In multivariate logistic regression analysis, individuals in the lowest tertile (T1) of 5-mC% had higher risk of RCC with OR of 1.40 (95%CI 1.06–1.84), compared to individuals in the highest tertile (T3) (Pfor trend=0.02). When stratified by RCC risk factors, associations between hypomethylation and increased RCC risk appeared to be stronger among males (OR=1.61, Pfor trend=0.01), younger age (OR=1.47, Pfor trend=0.03), never smokers (OR=1.55, Pfor trend=0.02), family history of other cancer (OR=1.64, Pfor trend=1.22E-03) and late stage (OR=2.06, Pfor trend=4.98E-04). Additionally, we observed significant interaction between gender and 5-mC% in elevating RCC risk (Pfor interaction=0.03). Our findings suggest an association between global DNA hypomethylation and RCC risk. To establish global DNA hypomethylation as a risk factor for RCC, future prospective studies are warranted. This study may provide further understanding of the etiology of RCC tumorigenesis.