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01-07-2012 | Translational Research and Biomarkers

Putatively Functional PLCE1 Variants and Susceptibility to Esophageal Squamous Cell Carcinoma (ESCC): A Case–Control Study in Eastern Chinese Populations

Authors: Haichuan Hu, MD, Jingmin Yang, PhD, Yihua Sun, MD, Yajun Yang, PhD, Ji Qian, PhD, Li Jin, PhD, Mengyun Wang, PhD, Rui Bi, MD, Ruoxin Zhang, MS, Meiling Zhu, PhD, Menghong Sun, MD, PhD, Hongxia Ma, PhD, Qingyi Wei, MD, PhD, Guoliang Jiang, MD, Xiaoyan Zhou, MD, PhD, Haiquan Chen, MD

Published in: Annals of Surgical Oncology | Issue 7/2012

Abstract

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 G_rs2274223C_rs11187870 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.

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Title: Putatively Functional PLCE1 Variants and Susceptibility to Esophageal Squamous Cell Carcinoma (ESCC): A Case–Control Study in Eastern Chinese Populations
Authors: Haichuan Hu, MD
Jingmin Yang, PhD
Yihua Sun, MD
Yajun Yang, PhD
Ji Qian, PhD
Li Jin, PhD
Mengyun Wang, PhD
Rui Bi, MD
Ruoxin Zhang, MS
Meiling Zhu, PhD
Menghong Sun, MD, PhD
Hongxia Ma, PhD
Qingyi Wei, MD, PhD
Guoliang Jiang, MD
Xiaoyan Zhou, MD, PhD
Haiquan Chen, MD
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 7/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2160-y

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Putatively Functional PLCE1 Variants and Susceptibility to Esophageal Squamous Cell Carcinoma (ESCC): A Case–Control Study in Eastern Chinese Populations

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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