Association between PLCε1 gene polymorphisms and susceptibility to esophageal carcinoma
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摘要:
目的 探讨PLCε1基因rs2274223 A/G单核苷酸多态性(single nucleotide polymorphism，SNP)和rs11599672 T/G SNP与河北省磁县高发区人群食管鳞状细胞癌(esophageal squamous cell carcinoma，ESCC)遗传易感性之间的关系。 方法 采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction，PCR-LDR)方法对527例ESCC患者和527例健康对照PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行基因分型。 结果 ESCC患者组上消化道肿瘤(upper gastrointestinal cancer，UGIC)家族史阳性个体比例为48.6%，显著高于健康对照组(39.3%，χ2=9.25，P=0.002)。ESCC患者组及健康对照组PLCε1基因rs2274223 A/G SNP AA、AG、GG基因型频率分别为48.0%、43.9%、8.1%和57.1%、37.5%、5.4%。与AA基因型相比，携带AG、GG、AG/GG基因型可能增加ESCC的发病风险，经年龄、性别、吸烟状况、UGIC家族史校正后的OR值分别为1.41(95%CI=1.09~ 1.83)、1.71(95%CI=1.03~2.86)、1.45(95%CI=1.13~1.85)。PLCε1基因rs11599672 T/G SNP等位基因频率和基因型频率总体分布在ESCC患者组及健康对照组之间无显著性差异(P>0.05)。应用2LD软件对PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行联合分析显示，两个多态性位点间不存在连锁不平衡现象(D'=0.11)。与最常见的AT单体型相比，GT单体型增加了ESCC的发病风险(OR=1.36，95%CI=1.08~1.71)。 结论 PLCε1基因rs2274223 A/G SNP可以作为高发区人群ESCC遗传易感性的标志物。UGIC家族史阳性个体、携带PLCε1基因rs2274223 A/G SNP AG、GG基因型的个体罹患ESCC的风险较高，应定期接受食管内镜检查，以便真正实现ESCC的早期诊断、早期治疗。 Abstract:Objective To explore the association of PLCε1 gene rs2274223 A/G single nucleotide polymorphism (SNP) and rs11599672 T/G SNP with susceptibility to esophageal squamous cell carcinoma (ESCC) in a population of Ci County high-incidence region in Hebei Province. Methods The genotypes of PLCε1 gene rs2274223 A/G SNP and rs11599672 T/G SNP were determined by polymerase chain reaction–ligase detection reaction method in 527 ESCC patients and 527 healthy controls. Results The frequency of positive family history of upper gastrointestinal cancer UGIC in ESCC patients was 48.6%, which is significantly higher than that in the healthy controls (39.3%) (χ2=9.25, P=0.002). The AA, AG, and GG genotype frequencies of PLCε1 gene rs2274223 A/G SNP were 48.0%, 43.9%, 8.1% in the ESCC patients and 57.1%, 37.5%, 5.4% in the healthy controls, respectively. Compared with AA genotype, AG, GG, and AG/GG genotypes enhanced the risk of ESCC. The age, sex, smoking status, and UGIC family history-adjusted OR were 1.41 (95% CI=1.09-1.83), 1.71 (95% CI=1.03-2.86), and 1.45 (95% CI=1.13-1.85), respectively. No significant difference was observed in the frequency of the genotype and allele of PLCε1 gene rs11599672 T/G SNP between the ESCC cases and the controls (P>0.05). PLCε1 gene rs2274223 A/G SNP and rs11599672 T/G SNP were combined for analysis using a 2LD software. Results showed that no linkage disequilibrium exists between these two SNPs (D'=0.11). Compared with the most frequent AT haplotype, the GT haplotype significantly increased the risk of ESCC (OR=1.36, 95% CI=1.08-1.71). Conclusion PLCε1 gene rs2274223 A/G SNP might serve as a marker predicting genetic susceptibility to ESCC of the population from Ci County. The subjects with UGIC family history and the AGor GG-genotype carriers had higher risk of ESCC and should receive periodic upper gastrointestinal fiber tests for early detection and treatment of ESCC. -
表 1 ESCC患者与健康对照者特征分布 n (%)
Table 1. Distribution of selected characteristics of ESCC patients and healthy controls
表 2 PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP与ESCC易感性的关系 n (%)
Table 2. Correlation of PLCε1 gene rs2274223 A/G SNP and rs11599672 T/G SNP to susceptibility of ESCC
表 3 PLCε1基因rs2274223 A/G SNP与ESCC发病风险关系的分层分析
Table 3. Stratification analysis for the association between PLCε1 gene rs2274223 A/G SNP and ESCC risk
表 4 PLCε1基因rs11599672 T/G SNP与ESCC发病风险关系的分层分析
Table 4. Stratification analysis for the associations between PLCε1gene rs11599672 T/G SNP and ESCC risk
表 5 PLCε1基因单体型与ESCC发病风险 n (%)
Table 5. PLCε1 gene haplotype and ESCC risk
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