Qu Y, Zhang S, Cui L, Wang K, Song C, Wang P, Zhang J, Dai L
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
Key Laboratory of Tumor Epidemiology, Zhengzhou, China.
Dis Esophagus. 2017 Jan 1;30(1):1-7. doi: 10.1111/dote.12463.
Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. Phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. To evaluate the association between the single nucleotide polymorphisms (SNPs) in PLCE1 gene and ESCC risk, a case-control study including 550 patients with ESCC and 550 age, gender-matched controls was carried out to investigate the genetic susceptibility of three SNPs (rs3765524 C/T and two unreported potentially functional SNPs rs10882379 G/A and rs829232 G/A) as well as the interactions of gene-gene and gene-environment in the development of ESCC. And the results showed that GA genotype of rs10882379 was significantly associated with reduced ESCC risk compared with GG genotype (adjusted OR [95% CI]: 0.66 [0.51, 0.86]), while AA genotype of rs829232 was significantly associated with increased ESCC risk compared with GG genotype (adjusted OR [95% CI]: 1.37 [1.12, 1.67]). The haplotype analysis showed increased ESCC risk in Grs10882379Crs3765524Ars829232 and Grs10882379Trs3765524Ars829232 haplotypes with OR (95% CI) of 1.40 (1.13, 1.73) and 1.66 (1.18, 2.34), respectively and inversely reduced ESCC risk in Ars10882379Crs3765524Grs829232 haplotype with OR (95% CI) of 0.74 (0.61, 0.91). The gene-environment interaction analysis emerged a best model consisted of four factors (rs10882379, rs3765524, rs829232 and family history of ESCC) that could increase the ESCC risk in the 'high risk group' with 4.45-fold (OR [95% CI]: 5.45 [4.13, 7.19]), compared to the 'low risk group.' Our results further validate that the SNPs in PLCE1 gene may contribute to the ESCC susceptibility in Chinese Han population. Also the gene-gene and gene-environment interactions play a certain crucial role in the ESCC progression.
食管癌是全球癌症相关死亡的第六大主要原因。通过针对中国人群的三项大规模全基因组关联研究（GWAS）发现，磷脂酶Cε1（PLCE1）基因与食管鳞状细胞癌（ESCC）风险相关。为评估PLCE1基因单核苷酸多态性（SNP）与ESCC风险之间的关联，开展了一项病例对照研究，纳入550例ESCC患者及550名年龄、性别匹配的对照，以研究三个SNP（rs3765524 C/T以及两个未报道的潜在功能性SNP rs10882379 G/A和rs829232 G/A）的遗传易感性，以及ESCC发生过程中的基因-基因和基因-环境相互作用。结果显示，与GG基因型相比，rs10882379的GA基因型与ESCC风险降低显著相关（校正OR[95%CI]：0.66[0.51,0.86]），而rs829232的AA基因型与GG基因型相比，与ESCC风险增加显著相关（校正OR[95%CI]：1.37[1.12,1.67]）。单倍型分析显示，Grs10882379Crs3765524Ars829232和Grs10882379Trs3765524Ars829232单倍型的ESCC风险增加，OR（95%CI）分别为1.40（1.13,1.73）和1.66（1.18,2.34），而Ars10882379Crs3765524Grs829232单倍型的ESCC风险降低，OR（95%CI）为0.74（0.61,0.91）。基因-环境相互作用分析得出一个最佳模型，该模型由四个因素（rs10882379、rs3765524、rs829232和ESCC家族史）组成，与“低风险组”相比，该模型可使“高风险组”的ESCC风险增加4.45倍（OR[95%CI]：5.45[4.13,7.19]）。我们的结果进一步证实，PLCE1基因中的SNP可能与中国汉族人群的ESCC易感性有关。此外，基因-基因和基因-环境相互作用在ESCC进展中起着一定的关键作用。
