A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer risk and telomere length.

A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer risk and telomere length.
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CYP1B1 中的单核苷酸多态性会导致前列腺癌风险和端粒长度的差异。

DOI:
10.7150/jca.21774
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发表时间:
2018
期刊:
影响因子:
3.9
通讯作者:
Ye DW
Ye DW
中科院分区:
医学3区
文献类型:
--
作者:
Gu CY;Li GX;Zhu Y;Xu H;Zhu Y;Qin XJ;Bo D;Ye DW

文献摘要

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背景:细胞色素P450 1B 1(CYP 1B 1)是雌激素代谢途径中的关键酶,参与羟化和结合。CYP 1B 1内功能相关的遗传变异可能会影响端粒长度,并随后导致前列腺癌的发生。方法:我们评估了1015名前列腺癌(PCa)患者和1052名无癌对照者的8种CYP 1B 1标签单核苷酸多态性(SNP),并计算比值比(OR)和95%置信区间(CI),以估计其与PCa风险的相关性。然后使用实时PCR在外周血白细胞中评估CYP 1B 1 SNP对相对端粒长度的影响。研究结果:CYP 1B 1 rs 1056836变异与PCa风险降低相关[比值比(OR):0.80; 95%置信区间(CI):0.68-0.99,P = 0.041]。端粒长度越长,CYP 1B 1 rs 1056836 CG/GG基因型的比例越高(OR:1.60,95%CI:1.04-2.45)。结论:我们的研究结果表明,CYP 1B 1内的遗传变异可能通过改变端粒长度赋予PCa遗传易感性。
BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Functionally relevant genetic variants within CYP1B1 may affect the telomere length and subsequently lead to prostate carcinogenesis. METHODS: We evaluated 8 CYP1B1 tag single nucleotide polymorphisms (SNPs) in 1015 men with prostate cancer (PCa) and 1052 cancer-free controls, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate their association with risk of PCa. The influence of CYP1B1 SNPs on the relative telomere lengths was then appraised in peripheral blood leukocytes using real-time PCR. RESULTS: CYP1B1 rs1056836 variant was associated with decreased risk of PCa [odds ratio (OR): 0.80; 95% confidence interval (CI): 0.68-0.99, P = 0.041]. Longer telomere length showed a significantly higher proportion of the CYP1B1 rs1056836 CG/GG genotypes, compared with that of the CC genotype (OR: 1.60, 95% CI: 1.04-2.45). CONCLUSION: Our findings suggest that genetic variants within CYP1B1 may confer genetic susceptibility to PCa by altering telomere length.
DOI: 10.18632/oncotarget.4980
发表时间: 2015-10-13
期刊: Oncotarget
影响因子: --
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发表时间: 2008-09
期刊: Carcinogenesis
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