Genetic variants in MUC4 gene are associated with lung cancer risk in a Chinese population.
Genetic variants in MUC4 gene are associated with lung cancer risk in a Chinese population.
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MUC4 基因的遗传变异与中国人群的肺癌风险相关
DOI：
10.1371/journal.pone.0077723
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Zhang Z;Wang J;He J;Zheng Z;Zeng X;Zhang C;Ye J;Zhang Y;Zhong N;Lu W
粘蛋白MUC4由MUC4基因编码，在上皮细胞增殖和分化中发挥重要作用。异常的 MUC4 过表达与侵袭性肿瘤增殖和上皮癌的不良预后相关。总的来说，现有证据表明 MUC4 具有肿瘤促进功能。在这项研究中，我们对中国人群中的 1,048 例肺癌病例和 1,048 例年龄和性别频率匹配的无癌对照进行了病例对照研究，以调查 MUC4 基因多态性在肺癌病因学中的作用。我们确定了 9 个与肺癌风险增加显着相关的 SNP（rs863582 的 P = 0.0425、rs842226 的 0.0333、rs842225 的 0.0294、rs2550236 的 0.0010、rs2688515 的 0.0149、rs 0.0191 2641773、加性模型中 rs3096337 为 0.0058、rs859769 为 0.0077、rs842461 为 0.0059）。与这些单基因座分析结果一致，单倍型分析揭示了rs3096337、rs859769和rs842461的单倍型“GGC”对肺癌的不利影响。 rs863582、rs842226、rs2550236、rs842225和rs2688515的单倍型和双倍型“CTGAGC”均对肺癌产生不良影响，这也与单位点分析一致。此外，我们观察到重度吸烟者中 rs863582 和 rs842461 存在统计学上显着的相互作用。我们的结果表明 MUC4 基因多态性及其与吸烟的相互作用可能有助于肺癌病因学。
Mucin MUC4, which is encoded by the MUC4 gene, plays an important role in epithelial cell proliferation and differentiation. Aberrant MUC4 overexpression is associated with invasive tumor proliferation and poor outcome in epithelial cancers. Collectively, the existing evidence suggests that MUC4 has tumor-promoter functions. In this study, we performed a case-control study of 1,048 incident lung cancer cases and 1,048 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of MUC4 gene polymorphism in lung cancer etiology. We identified nine SNPs that were significantly associated with increased lung cancer risk (P = 0.0425 for rs863582, 0.0333 for rs842226, 0.0294 for rs842225, 0.0010 for rs2550236, 0.0149 for rs2688515, 0.0191 for rs 2641773, 0.0058 for rs3096337, 0.0077 for rs859769, and 0.0059 for rs842461 in an additive model). Consistent with these single-locus analysis results, the haplotype analyses revealed an adverse effect of the haplotype “GGC” of rs3096337, rs859769, and rs842461 on lung cancer. Both the haplotype and diplotype “CTGAGC” of rs863582, rs842226, rs2550236, rs842225, and rs2688515 had an adverse effect on lung cancer, which is also consistent with the single-locus analysis. Moreover, we observed statistically significant interactions for rs863582 and rs842461 in heavy smokers. Our results suggest that MUC4 gene polymorphisms and their interaction with smoking may contribute to lung cancer etiology.
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影响因子：
8
作者：
Andrianifahanana, M;Agrawal, A;Batra, SK
通讯作者：
Batra, SK
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通讯作者：
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作者：
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Altshuler, D