A functional SNP rs1892901 in FOSL1 is associated with gastric cancer in Chinese population.
A functional SNP rs1892901 in FOSL1 is associated with gastric cancer in Chinese population.
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FOSL1 中的功能性 SNP rs1892901 与中国人群胃癌相关
DOI：
10.1038/srep41737
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发表时间：
2017-02-07
影响因子：
4.6
通讯作者：
Fan Z
中科院分区：
文献类型：
--
作者：
Liu W;Tian T;Liu L;Du J;Gu Y;Qin N;Yan C;Wang Z;Dai J;Fan Z
FOSL 1（FOS like antigen 1）是一种原癌基因，在多种肿瘤的发生发展中起重要作用。但FOSL 1基因SNPs与胃癌关系的研究尚缺乏。因此，我们采用病例对照设计，采用两阶段策略（筛选阶段：1，140例胃癌病例和1，547例对照;复制阶段：1，006例病例和2，273例对照）研究FOSL 1中7个SNP与胃癌的关联。在相加模型中发现rs 1892901与第一阶段胃癌发病风险显著相关（校正OR = 1.25，95%CI：1.06- 1.47，P = 0.008）。计算机模拟结果表明，rs 1892901可能改变多个调控基序，干扰蛋白结合，影响FOSL 1和其他重要的胃癌相关基因如EGR 1、CHD、EP 300、FOS、结果提示FOSL 1基因的功能性SNP rs 1892901可能影响FOSL 1基因的表达，从而增加胃癌的发生风险。进一步的功能研究和大规模人群研究是必要的，以证实我们的研究结果。
FOSL1(FOS like antigen 1) is one kind of proto-oncogene, and may play a vital role in carcinogenesis of multiple cancers. However, studies about the relationship between SNPs inFOSL1and gastric cancer are still lacking. Thus, we investigated the association of seven SNPs inFOSL1with gastric cancer using case-control design in a two-stage strategy (Screening stage: 1,140 gastric cancer cases and 1,547 controls; Replication stage: 1,006 cases and 2,273 controls). We found that rs1892901 was significantly associated with increased risk of gastric cancer in additive model (adjusted OR = 1.25, 95%CI: 1.06–1.47,P = 0.008) in first stage. Following replication results revealed that the relationship between rs1892901 and gastric cancer risk was consistent with our primary results.In silicoanalysis showed that rs1892901 might alter multiple regulatory motifs, disturb protein binding, and affect the expression ofFOSL1and other important gastric cancer-related genes such asEGR1, CHD, EP300, FOS, JUNandFOSL2.Our findings indicated that functional SNP rs1892901 inFOSL1might affect the expression ofFOSL1, and ultimately increase the risk of gastric cancer. Further functional studies and large-scale population studies are warranted to confirm our findings.