5个遗传性变型与前列腺癌的累积相关性

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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.
背景：5个染色体区域的单核苷酸多态性（SNPs）－3个在8q24上，另外两个分别在17q12 和 17q24.3上－与前列腺癌相关联，单个SNP只有中等程度相关，但多个SNPs组合时，相关性增强。
方法：我们从瑞典人的5个染色体区域中评价16个SNPs,(2893个前列腺癌患者和1781个对照)并明确SNPs与前列腺癌的单个和联合关系。
结果：在单SNPs分析中，在5个区域中的每一个区域中，有多个SNPs均与前列腺癌相关。当将5个区域中的每个相关性最显著的SNP选择同时包括进多变量分析中时，每个SNP在其他SNPs和家族史进行校正后仍保持着显著性相关。总之，5个SNPs和家族史可用来解释我们研究的46％瑞典男性前列腺癌病例。5个SNPs加上家族史与前列腺癌有一个累计的关联。具备任意5个或以上这些与前列腺癌相关的因素的男性，与不含任何因素的男性相比，患前列腺癌的优势比为9.46。这些变量和家族史的累积效应是不依赖诊断时PSA血清水平而独立的。
结论：五个染色体区域的SNPs加上前列腺癌家族史与前列腺癌有一个累积和显著的相关性。每个SNP和家族史的累积效应，就是说每增加一个SNP，prostate cancer风险就可能增加。




他们做出的只是一种标签
也许他本身是治病性的，也有的只是一种
指示，因为和他在同一个block中是共连锁的
真正的致病位点也许在他附近，具体说的积累效应
一般是指多个微效的突变位点累加可以加大疾病的易感性
不过有的也许是假阳性只是增加了关联分析过程中的相关性