Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study.
Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study.
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DOI：
10.1158/0008-5472.can-09-0648
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发表时间：
2009-12-15
期刊：
影响因子：
11.2
通讯作者：
Stanford JL
中科院分区：
文献类型：
--
作者：
Zhu Y;Stevens RG;Hoffman AE;Fitzgerald LM;Kwon EM;Ostrander EA;Davis S;Zheng T;Stanford JL
昼夜节律基因负责维持24小时昼夜节律的古老适应，并影响各种癌症相关的生物学途径，包括性激素水平的调节。然而，很少有研究调查昼夜节律基因在前列腺癌发展中的作用，前列腺癌是男性中最常见的癌症类型（不包括非黑色素瘤皮肤癌）。目前的遗传关联研究通过对10个昼夜节律相关基因中的41个标签和氨基酸改变SNP进行基因分型来测试与前列腺癌相关的昼夜节律基因假设，该研究在高加索男性中进行了基于人群的病例对照研究（N= 1，308例病例和1，266例对照）。我们的研究结果表明，在9个核心昼夜节律基因中至少有一个SNP，（PER 1中的rs885747和rs2289591，PER 2中的rs7602358，PER 3中的rs1012477，CSNK1E中的rs1534891，ARNTL中的rs12315175，ARNT2中的rs2292912，ARNTL中的rs7950226，CLOCK中的rs11133373，NPAS2中的rs1369481、rs895521和rs17024926）与前列腺癌的易感性显著相关（总体风险或侵袭性疾病风险），以及三个基因中四个SNP的风险估计。（PER 1中的rs885747和rs2289591，PER 3中的rs1012477和CLOCK中的rs11133373）因疾病侵袭性而异。单倍型的进一步分析与这些基因分型结果一致。这项候选基因关联研究的结果支持昼夜节律基因的遗传变异与前列腺癌风险之间存在联系的假设，从而进一步证实了前列腺肿瘤发生中昼夜节律生物标志物的机制研究。
Circadian genes are responsible for maintaining the ancient adaptation of a 24-hour circadian rhythm and influence a variety of cancer-related biological pathways, including the regulation of sex hormone levels. However, few studies have been undertaken to investigate the role of circadian genes in the development of prostate cancer, the most common cancer type among men (excluding non-melanoma skin cancer). The current genetic association study tested the circadian gene hypothesis in relation to prostate cancer by genotyping a total of 41 tagging and amino acid altering SNPs in ten circadian-related genes in a population-based case-control study of Caucasian men (N=1,308 cases and 1,266 controls). Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1, rs7602358 in PER2, rs1012477 in PER3, rs1534891 in CSNK1E, rs12315175 in CRY1, rs2292912 in CRY2, rs7950226 in ARNTL, rs11133373 in CLOCK, and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3 and rs11133373 in CLOCK) varied by disease aggressiveness. Further analyses of haplotypes were consistent with these genotyping results. Findings from this candidate gene association study support the hypothesis of a link between genetic variants in circadian genes and prostate cancer risk, warranting further confirmation and mechanistic investigation of circadian biomarkers in prostate tumorigenesis.