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中国北方京津冀地区居民中与前列腺癌相关的8q21和8q24基因变异研究。

Study of genetic variants of 8q21 and 8q24 associated with prostate cancer in Jing-Jin residents in northern China.

作者信息

Hui Juan, Xu Yong, Yang Kuo, Liu Ming, Wei Dong, Wei Dong, Zhang Yaoguang, Shi Xiao Hong, Yang Fan, Wang Nana, Zhang Yurong, Wang Xin, Liang Siying, Chen Xin, Sun Liang, Zhu Xiaoquan, Zhu Ling, Yang Yige, Tang Lei, Zhang Yuhong, Yang Ze, Wang Jianye

出版信息

Clin Lab. 2014;60(4):645-52. doi: 10.7754/clin.lab.2013.130624.

Abstract

BACKGROUND

To identify the genetic risk of six genetic variants at 8q21 and 8q24 (including rs1512268, A; rs12543663, C; rs10086908, C; rs1016343, T; rs13252298, A, and rs6983561, C) associated with prostate cancer in Beijing and Tianjin (Jing-jin) area residents in northern China.

METHODS

574 subjects were enrolled. Blood samples and clinical information were collected from histologically confirmed prostate cancer cases (n = 286) and clinically evaluated matched normal controls (n = 288) from Chinese men in northern China. Six SNPs at 8q21 and 8q24 were genotyped by high-resolution melt and sequencing in subjects. We compared statistical differences between the prevalence of risk genotypes with prostate cancer in cases and controls and analyzed the association between clinical covariates and risk loci in case groups to infer their relationship with aggressive prostate cancer.

RESULTS

Three genotypes of rs10086908, CC (OR = 2.48; 95% CI = 1.02 - 5.98, p = 0.037) rs1016343, TT (OR = 1.64, 95% CI = 1.07 - 2.53, p = 0.023); and rs6983561, CC (OR = 1.91; 95% CI = 1.09 - 3.63, p = 0.044) at 8q24 were identified to be associated with prostate cancer risk in Jing-jin Chinese. The D' values of both two-locus haplotypes (T-A: rs1016343 vs. rs13252298; T-C: rs1016343 vs. rs6983561) were 0.907 and 0.859, respectively, the three-locus haplotype, only TAC constituted by the loci (rs1016343, T; rs13252298, A; rs6983561, C) was also associated with prostate cancer (p = 0.033), revealing rs1016343 vs. rs6983561 with significant differences between cases and controls. According to clinical covariates and odds ratios of risk genotypes relative to non-risk genotypes, rs6983561, CC was associated with age (OR = 2.5; 95% CI = 1.02 - 6.13, p = 0.039), and tumor aggressiveness (OR = 1.15; 95% Cl = 1.06 - 1.23, p = 0.013).

CONCLUSIONS

The loci including rs10086908, rs1016343, and rs6983561 at 8q24 could be associated with prostate cancer in Jing-jin residents in northern China. Our results suggest that these loci could influence susceptibility to prostate cancer in the northern Chinese population.

摘要

背景

确定位于8q21和8q24的六个基因变异(包括rs1512268,A;rs12543663,C;rs10086908,C;rs1016343,T;rs13252298,A和rs6983561,C)与中国北方京津地区居民前列腺癌的遗传风险。

方法

招募574名受试者。从中国北方男性经组织学确诊的前列腺癌病例(n = 286)和经临床评估匹配的正常对照(n = 288)中收集血样和临床信息。通过高分辨率熔解曲线分析和测序对受试者8q21和8q24的六个单核苷酸多态性(SNP)进行基因分型。我们比较了病例组和对照组中前列腺癌风险基因型患病率的统计学差异,并分析了病例组中临床协变量与风险位点之间的关联,以推断它们与侵袭性前列腺癌的关系。

结果

8q24的rs10086908的三种基因型,CC(比值比[OR] = 2.48;95%可信区间[CI] = 1.02 - 5.98,p = 0.037)、rs1016343的TT(OR = 1.64,95% CI = 1.07 - 2.53,p = 0.023);以及rs6983561的CC(OR = 1.91;95% CI = 1.09 - 3.63,p = 0.044)被确定与京津地区中国人的前列腺癌风险相关。两个位点单倍型(T-A:rs1016343与rs13252298;T-C:rs1016343与rs6983561)的D'值分别为0.907和0.859,三个位点单倍型,仅由位点(rs1016343,T;rs13252298,A;rs6983561,C)构成的TAC也与前列腺癌相关(p = 0.033),表明rs1016343与rs6983561在病例组和对照组之间存在显著差异。根据临床协变量以及风险基因型相对于非风险基因型的比值比,rs6983561的CC与年龄相关(OR = 2.5;95% CI = 1.02 - 6.13,p = 0.039),以及与肿瘤侵袭性相关(OR = 1.15;95% CI = 1.06 - 1.23,p = 0.013)。

结论

8q24包括rs10086908、rs1016343和rs6983561的位点可能与中国北方京津地区居民的前列腺癌相关。我们的结果表明这些位点可能影响中国北方人群对前列腺癌的易感性。

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