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甲硫氨酸合成酶(METH)基因中的单核苷酸多态性(rs1805087)会增加患前列腺癌的风险。

A single-nucleotide polymorphism (rs1805087) in the methionine synthase (METH) gene increases the risk of prostate cancer.

作者信息

Zhang Xiaosong, Tang Jilei, Shen Nan, Ren Kewei

机构信息

Department of Urology, Nantong Tongzhou District People's Hospital, Nantong 226300, China.

Department of Orthopedics, Qidong People's Hospital, Nantong 226200, China.

出版信息

Aging (Albany NY). 2018 Oct 18;10(10):2741-2754. doi: 10.18632/aging.101584.

DOI:10.18632/aging.101584
PMID:30337500
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6224252/
Abstract

Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of single-nucleotide polymorphism rs1805087 involving 12 independent case-control studies comprising 9986 prostate cancer patients and 40134 controls. The odds ratio and 95% confidence intervals were applied to evaluate the relation of this single-nucleotide polymorphism with prostate cancer. Statistical analysis was performed in STATA 11.0. A significant association was found between rs1805087 and increased prostate cancer risk, overall and with Hardy-Weinberg equilibrium. In subgroup analyses (based on ethnicity, source of control, genotyping methods, or publication status), similar associations were observed (e.g., genotype GA vs. AA: odds ratio 1.19, 95% confidence interval 1.01-1.40 among whites; G allele vs. A allele: odds ratio 1.14, 95% confidence interval 1.02-1.28 among hospital-based controls). Thus, the common polymorphism (rs1805087) of may be associated with increased prostate cancer risk. Further studies with a larger sample size and detailed gene-environment interactions should be conducted to identify the role of polymorphisms in prostate cancer susceptibility.

摘要

甲硫氨酸合成酶(METH,即MTR)是叶酸代谢途径中的关键酶,在DNA的合成、修复和甲基化过程中起关键作用。基因多态性与前列腺癌易感性之间的关联仍不明确。因此,我们对单核苷酸多态性rs1805087进行了一项更新的荟萃分析,该分析涉及12项独立的病例对照研究,共纳入9986例前列腺癌患者和40134例对照。采用优势比和95%置信区间来评估该单核苷酸多态性与前列腺癌的关系。在STATA 11.0软件中进行统计分析。结果发现,rs1805087与前列腺癌风险增加之间存在显著关联,总体上以及在哈迪-温伯格平衡状态下均如此。在亚组分析(基于种族、对照来源、基因分型方法或发表状态)中,也观察到了类似的关联(例如,在白人中,基因型GA与AA相比:优势比为1.19,95%置信区间为1.01 - 1.40;在以医院为基础的对照中,G等位基因与A等位基因相比:优势比为1.14,95%置信区间为1.02 - 1.28)。因此,该基因的常见多态性(rs1805087)可能与前列腺癌风险增加有关。应开展更大样本量以及详细的基因-环境相互作用的进一步研究,以确定该多态性在前列腺癌易感性中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/19999bd7aadb/aging-10-101584-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/8e21adec1cd7/aging-10-101584-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/1c868b9dd5a1/aging-10-101584-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/83de770bcd9f/aging-10-101584-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/027e0c457d5b/aging-10-101584-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/9a8a5e550c34/aging-10-101584-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/c37de6fe3704/aging-10-101584-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/21002994d58f/aging-10-101584-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/3f6f5096801c/aging-10-101584-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/19999bd7aadb/aging-10-101584-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/8e21adec1cd7/aging-10-101584-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/1c868b9dd5a1/aging-10-101584-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/83de770bcd9f/aging-10-101584-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/027e0c457d5b/aging-10-101584-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/9a8a5e550c34/aging-10-101584-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/c37de6fe3704/aging-10-101584-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/21002994d58f/aging-10-101584-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/3f6f5096801c/aging-10-101584-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/6224252/19999bd7aadb/aging-10-101584-g009.jpg

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Screening for prostate cancer.
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Functional variants of the 5-methyltetrahydrofolate-homocysteine methyltransferase gene significantly increase susceptibility to prostate cancer: Results from an ethnic Han Chinese population.5-甲基四氢叶酸-同型半胱氨酸甲基转移酶基因的功能变体显著增加前列腺癌的易感性:汉族人群的研究结果。
Sci Rep. 2016 Nov 3;6:36264. doi: 10.1038/srep36264.
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Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects.日本人群中叶酸代谢基因多态性与胰腺癌风险的关联。
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