磷脂酶Cε1（PLCE1 rs2274223A>G、rs3765524C>T和rs7922612C>T）基因多态性与克什米尔山谷地区食管癌风险

Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley.

作者信息

Malik Manzoor Ahmad, Umar Meenakshi, Gupta Usha, Zargar Showkat Ali, Mittal Balraj

机构信息

Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(10):4319-23. doi: 10.7314/apjcp.2014.15.10.4319.

DOI:10.7314/apjcp.2014.15.10.4319

PMID:24935391

Abstract

BACKGROUND

Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area.

MATERIALS AND METHODS

We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS.

RESULTS

The selected PLCE1 polymorphisms did not show independent association with EC. However, the G2274223T3765524T7922612 haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC.

CONCLUSIONS

Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.

摘要

背景

磷脂酶Cε1（PLCE1）编码磷脂酶家族的一种蛋白质，该家族在包括食管癌（EC）在内的多种癌症的发生和发展中起关键作用。在两项大规模全基因组关联研究（GWAS）中，PLCE1中的单核苷酸多态性（SNP，rs2274223A>G，rs3765524C>T）被确定为中国食管癌（EC）的新的易感位点。本研究的目的是在高风险地区克什米尔山谷调查这一发现。

材料与方法

我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对克什米尔山谷135例EC患者和195例年龄及性别匹配的对照者的PLCE1的三个潜在功能性SNP（rs2274223A>G、rs3765524C>T和rs7922612C>T）进行基因分型。使用SPSS通过二元逻辑回归估计发生EC的风险。