Prostate Cancer Susceptibility in Men of African Ancestry at 8q24
Prostate Cancer Susceptibility in Men of African Ancestry at 8q24
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DOI：
10.1093/jnci/djv431
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发表时间：
2016-07-01
影响因子：
10.3
通讯作者：
Haiman, Christopher A.
中科院分区：
文献类型：
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作者：
Han, Ying;Rand, Kristin A.;Haiman, Christopher A.
8 q24区域包含不同癌症的多种风险变体，包括前列腺癌的> 8。在这项研究中，我们对8 q24风险区域（127.8-128.8 Mb）进行了精细定位，以寻找4853例前列腺癌病例患者和4678例非洲血统对照受试者中常见和罕见变异的新关联。所有统计检验均为双侧检验。我们确定了P值小于5.00 × 10（-8）的三个独立关联，所有这些都在加纳和乌干达的研究中得到了重复（合并样本= 5869例病例患者，5615例对照受试者; rs 114798100：风险等位基因频率[RAF] = 0.04，每等位基因比值比[OR] = 2.31，95%置信区间[CI] = 2.04至2.61，P = 2.38 x 10（-40）; rs72725879：RAF = 0.33，OR = 1.37，95%CI = 1.30至1.45，P = 3.04 x 10（-27）; rs111906932：RAF = 0.03，OR = 1.79，95%CI = 1.53至2.08，P = 1.39 x 10（-13））。风险变体rs 114798100和rs 111906923仅在非洲血统的男性中发现，rs 111906923代表一种新的关联信号。这三种变体位于许多前列腺癌相关的长非编码RNA（lncRNA）内或附近，包括PRNCR 1，PCAT 1和PCAT 2。这些发现突出了祖先特异性风险变异，并涉及8 q24前列腺癌易感区域的前列腺特异性lncRNA。
The 8q24 region harbors multiple risk variants for distinct cancers, including > 8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8 Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00 x 10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38 x 10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04 x 10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39 x 10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.