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【medical-news】NEJM:5个SNP累积效应导致前列腺癌

Cumulative Association of Five Genetic Variants with Prostate Cancer

ABSTRACT

Background
Single-nucleotide polymorphisms (SNPs) in five chromosomal regions — three at 8q24 and one each at 17q12 and 17q24.3 — have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger.

Methods
We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer.

Results
Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93x10–28). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P=1.29x10–8), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis.

Conclusions
SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.

http://content.nejm.org/cgi/content/short/358/9/910 认领了! 第一次翻译,请多指教。

5处前列腺癌相关基因变异存在累积协同效应
摘要
背景
5个染色体区域(3个在8 q24区域,17q12和17q24.3各1)的单核苷酸多态性位点(SNPs )被认为和前列腺癌的发生相关。每个SNP对前列腺癌的引发作用相对有限,但是,当多个SNP同时存在,将会发生累积协同效应。
方法
我们评估了来自5个染色体区域的16处SNPs,样本来自瑞典人群( 2893名前列腺癌患者和1781名正常对照人群) ,并就SNP对引发前列腺癌的个体效应和协同效应进行了评估。
结果
在对单个SNP的分析中,5个染色体区域内的多个SNP位点被证实与前列腺癌的发生相关。
当其中最有意义的SNP位点被纳入多元统计分析时,结果显示经其他SNPs位点和前列腺癌家族史的校正,每个SNP位点在前列腺癌发生机制中的作用仍然显著。
5个SNPs位点和家族史这两个因素一起,占本研究中患有前列腺癌瑞典人群的46%。5个单核苷酸多态性和家族史对前列腺癌的发生存在累积协同作用( P for trend, 3.93x10 - 28 ) 。有其中任意5个或更多因素的瑞典男子,与完全没有这些因素的男子相比,其发生前列腺癌的OR值为9.46( P = 1.29x10 - 8 )。在诊断中,这些变异的累积效应和家族史是独立于血清前列腺特异性抗原之外的因素。
结论
5个染色体区域内的SNPs位点和家族史对前列腺癌的发生有累积效应和显着的协同效应。

The New England Jounal of Medicine, 2008, 358:910-919
作者:Center for Human Genomics (S.L.Z., J.S., S.S., G.L., F.-C.H., Y.Z., A.R.T., W.L., E.R.B., D.A.M., B.-L.C., J.X.) and the Departments of Biostatistical Sciences (F.-C.H.) and Urology (A.K.K.), Wake Forest University School of Medicine, Winston-Salem, NC; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (F.W., H.-O.A., K.B., H.G.); the Department of Urology, Umeå University Hospital, Umeå, Sweden (P.S.); the Department of Epidemiology, Harvard School of Public Health, Boston (H.-O.A.); Translational Genomics Research Institute, Phoenix, AZ (D.D., J.D.C.); and Johns Hopkins Medical Institutions, Baltimore (W.B.I.).
中文字数:502 哪五个基因的snp啊?

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作者:admin@医学,生命科学    2010-10-22 22:06
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