BACKGROUND: A novel variant rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with risk of esophageal squamous cell carcinoma (ESCC) by 2 large-scale genome-wide association studies (GWASs) in Chinese populations. In this study, we aimed to assess such an association in an eastern Chinese population and to address its possibly functional role in the etiology of ESCC. METHODS: A total of 1061 ESCC cases and 1211 controls were recruited and successfully genotyped for 2 single nucleotide polymorphisms (SNPs) (rs2274223 and rs11187870) of the PLCE1 gene by the TaqMan assay. Real-time PCR and immunohistochemical (IHC) analysis were applied to assess mRNA and protein expression levels, respectively, in a subset of tumor samples. RESULTS: SNP rs2274223 was independently associated with risk of ESCC (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.03-2.17 for GG vs AA), and SNP rs11187870 was also found to be associated with risk of ESCC assuming a dominant model (adjusted OR, 1.20; 95% CI, 1.00-1.44 for CG/CC vs GG). The Grs2274223Crs11187870 haplotype increased the risk for ESCC by 1.22-fold (95% CI, 1.04-1.42). Further experiments showed that overall PLCE1 mRNA expression was lower in tumor than in paired normal tissues (0.067±0.016 vs 0.264±0.067, P<.05), and the IHC analysis showed the normal tissues of rs2274223 GG genotype had a lower PLCE1 staining score than that of the AG genotype (0.40±0.22 vs 1.33±0.32, P<.05). CONCLUSIONS: PLCE1 SNP rs2274223 A>G change may reduce gene expression, and the variant G genotypes might contribute to risk of ESCC.
BACKGROUND: A novel variant rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with risk of esophageal squamous cell carcinoma (ESCC) by 2 large-scale genome-wide association studies (GWASs) in Chinese populations. In this study, we aimed to assess such an association in an eastern Chinese population and to address its possibly functional role in the etiology of ESCC. METHODS: A total of 1061 ESCC cases and 1211 controls were recruited and successfully genotyped for 2 single nucleotide polymorphisms (SNPs) (rs2274223 and rs11187870) of the PLCE1 gene by the TaqMan assay. Real-time PCR and immunohistochemical (IHC) analysis were applied to assess mRNA and protein expression levels, respectively, in a subset of tumor samples. RESULTS: SNP rs2274223 was independently associated with risk of ESCC (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.03-2.17 for GG vs AA), and SNP rs11187870 was also found to be associated with risk of ESCC assuming a dominant model (adjusted OR, 1.20; 95% CI, 1.00-1.44 for CG/CC vs GG). The Grs2274223Crs11187870 haplotype increased the risk for ESCC by 1.22-fold (95% CI, 1.04-1.42). Further experiments showed that overall PLCE1 mRNA expression was lower in tumor than in paired normal tissues (0.067±0.016 vs 0.264±0.067, P<.05), and the IHC analysis showed the normal tissues of rs2274223 GG genotype had a lower PLCE1 staining score than that of the AG genotype (0.40±0.22 vs 1.33±0.32, P<.05). CONCLUSIONS:PLCE1 SNP rs2274223 A>G change may reduce gene expression, and the variant G genotypes might contribute to risk of ESCC.
Authors: Wen-Qing Li; Nan Hu; Victoria H Burton; Howard H Yang; Hua Su; Catherine M Conway; Lemin Wang; Chaoyu Wang; Ti Ding; Yi Xu; Carol Giffen; Christian C Abnet; Alisa M Goldstein; Stephen M Hewitt; Philip R Taylor Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-05-27 Impact factor: 4.254
Authors: Hannah Bye; Natalie J Prescott; Cathryn M Lewis; Marco Matejcic; Loven Moodley; Barbara Robertson; Christo van Rensburg; M Iqbal Parker; Christopher G Mathew Journal: Carcinogenesis Date: 2012-08-03 Impact factor: 4.944
Authors: Xiao-Bin Cui; Xue-Lian Pang; Su Li; Jing Jin; Jian-Ming Hu; Lan Yang; Chun-Xia Liu; Li Li; Shu Jun Wen; Wei-Hua Liang; Yun-Zhao Chen; Feng Li Journal: Med Oncol Date: 2013-12-05 Impact factor: 3.064