Molecular Biology Reports

, Volume 39, Issue 9, pp 9105–9111 | Cite as

Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population

  • Haiyong Gu
  • Guowen Ding
  • Wenbo Zhang
  • Chao Liu
  • Yijang Chen
  • Suocheng Chen
  • Pengcheng Jiang


Esophageal cancer is one of the most aggressive cancers in the world. Recent large-scale genome-wide association studies (GWAS) reported that functional genetic variations in the phospholipase C epsilon gene (PLCE1) were strongly associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in Chinese population. For C20orf54 rs13042395 genotype and risk of esophageal cancer, the results were inconsistent. We conducted a replication case–control study to evaluate the genetic effects of these two functional single nucleotide polymorphisms (SNPs) on the development of esophageal cancer. A total of 380 cases and 380 controls were recruited for this study. The genotypes were determined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). The variant alleles of the functional polymorphism, PLCE1 rs2274223 SNP was associated with the increased risk of esophageal cancer [adjusted odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.05–3.59 for PLCE1 rs2274223 GG vs. AA]. However, there was no significant association between the C20orf54 rs13042395 genotype and esophageal cancer risk (adjusted OR = 0.99, 95 % CI = 0.63–1.57 for C20orf54 rs13042395 TT vs. CC). Stratified analyses indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 AG genotype was more evident among females, younger patients and never drinkers, compared with the PLCE1 rs2274223 AA genotypes. Stratified analyses also indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 GG genotype was more evident among never smokers and never drinkers compared with the PLCE1 rs2274223 AA genotypes. These findings indicated that functional polymorphisms PLCE1 rs2274223 might contribute to esophageal cancer susceptibility.


PLCE1, C20orf54 Polymorphisms Esophageal cancer Molecular epidemiology 



Confidential interval


Genome-wide association study


Linkage disequilibrium


Odds ratio


Single nucleotide polymorphisms



This study was supported in part by National Natural Science Foundation of China (81101889) and Social Development Foundation of Zhenjiang (SH2010017).


  1. 1.
    Shinomiya T, Mori T, Ariyama Y, Sakabe T, Fukuda Y, Murakami Y, Nakamura Y, Inazawa J (1999) Comparative genomic hybridization of squamous cell carcinoma of the esophagus: the possible involvement of the DPI gene in the 13q34 amplicon. Genes Chromosomes Cancer 24:337–344CrossRefPubMedGoogle Scholar
  2. 2.
    Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y, Liu Z, Zhan Q, Liu Y, Yu D, Zhai K, Chang J, Qiao Y, Jin G, Liu Z, Shen Y, Guo C, Fu J, Miao X, Tan W, Shen H, Ke Y, Zeng Y, Wu T, Lin D (2011) Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet 43:679–684CrossRefPubMedGoogle Scholar
  3. 3.
    Wang LD, Zhou FY, Li XM, Sun LD, Song X, Jin Y, Li JM, Kong GQ, Qi H, Cui J, Zhang LQ, Yang JZ, Li JL, Li XC, Ren JL, Liu ZC, Gao WJ, Yuan L, Wei W, Zhang YR, Wang WP, Sheyhidin I, Li F, Chen BP, Ren SW, Liu B, Li D, Ku JW, Fan ZM, Zhou SL, Guo ZG, Zhao XK, Liu N, Ai YH, Shen FF, Cui WY, Song S, Guo T, Huang J, Yuan C, Huang J, Wu Y, Yue WB, Feng CW, Li HL, Wang Y, Tian JY, Lu Y, Yuan Y, Zhu WL, Liu M, Fu WJ, Yang X, Wang HJ, Han SL, Chen J, Han M, Wang HY, Zhang P, Li XM, Dong JC, Xing GL, Wang R, Guo M, Chang ZW, Liu HL, Guo L, Yuan ZQ, Liu H, Lu Q, Yang LQ, Zhu FG, Yang XF, Feng XS, Wang Z, Li Y, Gao SG, Qige Q, Bai LT, Yang WJ, Lei GY, Shen ZY, Chen LQ, Li EM, Xu LY, Wu ZY, Cao WK, Wang JP, Bao ZQ, Chen JL, Ding GC, Zhuang X, Zhou YF, Zheng HF, Zhang Z, Zuo XB, Dong ZM, Fan DM, He X, Wang J, Zhou Q, Zhang QX, Jiao XY, Lian SY, Ji AF, Lu XM, Wang JS, Chang FB, Lu CD, Chen ZG, Miao JJ, Fan ZL, Lin RB, Liu TJ, Wei JC, Kong QP, Lan Y, Fan YJ, Gao FS, Wang TY, Xie D, Chen SQ, Yang WC, Hong JY, Wang L, Qiu SL, Cai ZM, Zhang XJ (2010) Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet 42:759–763CrossRefPubMedGoogle Scholar
  4. 4.
    Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkaloglu A, Cleper R, Basel-Vanagaite L, Pohl M, Griebel M, Tsygin AN, Soylu A, Muller D, Sorli CS, Bunney TD, Katan M, Liu J, Attanasio M, O’Toole JF, Hasselbacher K, Mucha B, Otto EA, Airik R, Kispert A, Kelley GG, Smrcka AV, Gudermann T, Holzman LB, Nurnberg P, Hildebrandt F (2006) Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet 38:1397–1405CrossRefPubMedGoogle Scholar
  5. 5.
    Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, Loirat C, Ozaltin F, Hashmi S, Ulmer F, Cleper R, Ettenger R, Antignac C, Wiggins RC, Zenker M, Hildebrandt F (2008) Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant 23:1291–1297CrossRefPubMedGoogle Scholar
  6. 6.
    Wing MR, Bourdon DM, Harden TK (2003) PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Mol Interv 3:273–280CrossRefPubMedGoogle Scholar
  7. 7.
    Harden TK, Sondek J (2006) Regulation of phospholipase C isozymes by ras superfamily GTPases. Annu Rev Pharmacol Toxicol 46:355–379CrossRefPubMedGoogle Scholar
  8. 8.
    Ada-Nguema AS, Xenias H, Hofman JM, Wiggins CH, Sheetz MP, Keely PJ (2006) The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLCepsilon. J Cell Sci 119:1307–1319CrossRefPubMedGoogle Scholar
  9. 9.
    Li M, Edamatsu H, Kitazawa R, Kitazawa S, Kataoka T (2009) Phospholipase cepsilon promotes intestinal tumorigenesis of Apc(Min/+) mice through augmentation of inflammation and angiogenesis. Carcinogenesis 30:1424–1432CrossRefPubMedGoogle Scholar
  10. 10.
    Bai Y, Edamatsu H, Maeda S, Saito H, Suzuki N, Satoh T, Kataoka T (2004) Crucial role of phospholipase cepsilon in chemical carcinogen-induced skin tumor development. Cancer Res 64:8808–8810CrossRefPubMedGoogle Scholar
  11. 11.
    Ou L, Guo Y, Luo C, Wu X, Zhao Y, Cai X (2010) RNA interference suppressing PLCE1 gene expression decreases invasive power of human bladder cancer T24 cell line. Cancer Genet Cytogenet 200:110–119CrossRefPubMedGoogle Scholar
  12. 12.
    Wang X, Zbou C, Qiu G, Fan J, Tang H, Peng Z (2008) Screening of new tumor suppressor genes in sporadic colorectal cancer patients. Hepatogastroenterology 55:2039–2044PubMedGoogle Scholar
  13. 13.
    Bourguignon LY, Gilad E, Brightman A, Diedrich F, Singleton P (2006) Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells. J Biol Chem 281:14026–14040CrossRefPubMedGoogle Scholar
  14. 14.
    Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, Yuan JM, Zheng W, Dawsey SM, Dong LM, Lee MP, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Wang C, Wheeler W, Gail MH, Yeager M, Yuenger J, Hutchinson A, Jacobs KB, Giffen CA, Burdett L, Fraumeni JF Jr, Tucker MA, Chow WH, Goldstein AM, Chanock SJ, Taylor PR (2010) A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet 42:764–767CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Schaeffeler E, Zanger UM, Eichelbaum M, Asante-Poku S, Shin JG, Schwab M (2008) Highly multiplexed genotyping of thiopurine s-methyltransferase variants using MALD-TOF mass spectrometry: reliable genotyping in different ethnic groups. Clin Chem 54:1637–1647CrossRefPubMedGoogle Scholar
  16. 16.
    Kelley GG, Reks SE, Ondrako JM, Smrcka AV (2001) Phospholipase C(epsilon): a novel Ras effector. EMBO J 20:743–754CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T (2001) Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras. J Biol Chem 276:2752–2757CrossRefPubMedGoogle Scholar
  18. 18.
    Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3:11–22CrossRefPubMedGoogle Scholar
  19. 19.
    Ma H, Wang LE, Liu Z, Sturgis EM, Wei Q (2011) Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck. BMC Cancer 11:258CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Wang X, Zhou C, Qiu G, Yang Y, Yan D, Xing T, Fan J, Tang H, Peng Z (2011) Phospholipase C epsilon plays a suppressive role in incidence of colorectal cancer. Med Oncol 2:1051–1058Google Scholar
  21. 21.
    Zhang H, Jin G, Li H, Ren C, Ding Y, Zhang Q, Deng B, Wang J, Hu Z, Xu Y, Shen H (2011) Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population. Carcinogenesis 32:848–852CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of Cardiothorac SurgeryAffiliated People’s Hospital of Jiangsu UniversityZhenjiangChina
  2. 2.Department of Thoracic & Cardiac SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  3. 3.Department of General SurgeryAffiliated People’s Hospital of Jiangsu UniversityZhenjiangChina

Personalised recommendations