HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese
HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese
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基于 HapMap 的研究确定了染色体 19q13.3 上与中国人肺癌相关的风险亚区域
DOI：
10.1016/j.canep.2013.09.016
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发表时间：
2013-12-01
影响因子：
2.6
通讯作者：
Ma, Jian
中科院分区：
文献类型：
--
作者：
Yin, Jiaoyang;Vogel, Ulla;Ma, Jian
背景：在之前的研究中，染色体 19q13.3 已被确定为与癌症风险相关的区域之一。方法：我们使用单倍型标记SNP（htSNP）方法和HapMap平台系统地检测了中国人染色体19q13.3上包含四个基因的70.772 kb区域。该研究涉及 339 例肺癌病例和 358 例非癌症对照病例。两个 htSNP（rs1046282 和 rs735482）捕获了 CD3EA 的大部分常见单倍型，16 个 htSNP 的综合作用提供了 ERCC2、PPP1R13L、CD3EAP 和 ERCC1 常见单倍型的高覆盖率。结果：CD3EAP rs735482 的变异 CC 基因型携带者 [调整后 OR (95% CI) = 1.28 (1.02-1.60)，P = 0.04] 和 20 年以上吸烟者中变异 C 等位基因 [OR (95% CI) = 2.13 (1.24-3.67)，P = 0.006] 患肺癌的风险增加。鉴定出四个强连锁不平衡的单倍型块。块 1 中的单倍型 ERCC2 rs3916874(G) 和 rs238415(C) [OR (95% CI) = 1.26 (1.02-1.57), P = 0.03] 和单倍型 PPP1R13L rs4803817(A)、CD3EAP rs1046282(T)，第 3 组中的 rs735482(C)、ERCC1 rs3212980(A)、rs3212964(G) [OR (95% CI) = 3.56 (1.55-8.18), P = 0.005] 与肺癌风险相关。 MDR（多因子降维）分析证明了包含吸烟时间和 ERCC1 中 rs2298881 的两个属性的最佳显着模型（P = 0.004-0.005），并表明吸烟时间和 ERCC2、PPP1R13、ERCC1 htSNP 之间的高阶相互作用的影响可以调节肺癌风险。结论：基于 HapMap 的 19q13.3 研究发现，CD3EAP 和两个基因座的遗传变异与肺癌风险相关，吸烟时间和遗传变异的相互作用是中国人群肺癌风险的最强预测因子。 (C) 2013 Elsevier Ltd. 保留所有权利。
Background: Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. Methods: We systematically examined the 70.772 kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. Results: Both carriers of variant CC genotype [adjusted OR (95% CI) = 1.28 (1.02-1.60), P = 0.04] and variant C-allele among >20 years' smokers [OR (95% CI) = 2.13 (1.24-3.67), P = 0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874(G) and rs238415(C) [OR (95% CI) = 1.26 (1.02-1.57), P = 0.03] in block 1 and the haplotype PPP1R13L rs4803817(A), CD3EAP rs1046282(T), rs735482(C), ERCC1 rs3212980(A), rs3212964(G) [OR (95% CI) = 3.56 (1.55-8.18), P = 0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P = 0.004-0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. Conclusions: HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population. (C) 2013 Elsevier Ltd. All rights reserved.