五种基因变异与前列腺癌的累积关联。

Cumulative association of five genetic variants with prostate cancer.

作者信息

Zheng S Lilly, Sun Jielin, Wiklund Fredrik, Smith Shelly, Stattin Pär, Li Ge, Adami Hans-Olov, Hsu Fang-Chi, Zhu Yi, Bälter Katarina, Kader A Karim, Turner Aubrey R, Liu Wennuan, Bleecker Eugene R, Meyers Deborah A, Duggan David, Carpten John D, Chang Bao-Li, Isaacs William B, Xu Jianfeng, Grönberg Henrik

机构信息

Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

出版信息

N Engl J Med. 2008 Feb 28;358(9):910-9. doi: 10.1056/NEJMoa075819. Epub 2008 Jan 16.

DOI:10.1056/NEJMoa075819

PMID:18199855

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.

摘要

背景

五个染色体区域的单核苷酸多态性（SNP）——8q24区域有三个，17q12和17q24.3区域各有一个——已被证实与前列腺癌相关。每个SNP的关联性都较为中等，但当这些SNP联合起来时，关联性可能更强。

方法

我们在瑞典人群（2893例前列腺癌患者和1781例对照者）中评估了来自五个染色体区域的16个SNP，并评估了这些SNP与前列腺癌的个体及联合关联性。

结果

在单SNP分析中，五个区域中的每一个区域的多个SNP都与前列腺癌相关。当从五个区域中各自选取最显著的SNP并纳入多变量分析时，在对其他SNP和家族史进行校正后，每个SNP仍然具有显著性。总体而言，我们研究的瑞典男性中，这五个SNP和家族史估计可解释46%的前列腺癌病例。这五个SNP加上家族史与前列腺癌存在累积关联性（趋势P值为3.93×10⁻²⁸）。与没有任何这些因素的男性相比，有任何五个或更多这些与前列腺癌相关因素的男性患前列腺癌的比值比为9.46（P = 1.29×10⁻⁸）。这些变异和家族史的累积效应独立于诊断时的血清前列腺特异性抗原水平。