An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1 rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms

  • Ziba Nariman-saleh-fam
  • Zahra Saadatian
  • Lida Nariman-Saleh-Fam
  • Elaheh Ouladsahebmadarek
  • Javad Tavakkoly-BazzazEmail author
  • Milad BastamiEmail author
Original Article


One of the highest risk of esophageal squamous cell carcinoma (ESCC) in the world has been reported in Iran, which is located in the Asian esophageal cancer belt. ESCC constitutes 90% of the esophageal cancer cases in Iran. Genome wide association studies (GWASs) in Chinese have identified a number of candidate variants, of which PLCE1rs2274223, C20orf54rs13042395 and RUNX1rs2014300 are studied in high risk populations including Chinese, Caucasians and Africans. However, results are inconsistent and it is unknown whether similar associations exist in Iranian population. We evaluated association of three GWAS identified variants with risk of ESCC in an Iranian cohort consisted of 200 ESCC patients and 300 healthy controls and conducted meta-analysis of ESCC risk associated with rs2274223 (involving 9810 cases and 13,128 controls) and rs13042395 (involving 2363 cases and 5329 controls). Logistic regression analysis showed that rs2274223 was associated with ESCC under codominant [GG/AA, 2.47(1.17–5.23), P:0.021], dominant [AG + GG/AA, 1.57(1.09–2.27), P:0.016], recessive [GG/AA+AG, 2.18(1.04–4.56), P:0.036] and log-additive models [1.51(1.12–2.02), P:0.006]. C20orf54 rs13042395 was not associated with ESCC under any genetic model. RUNX1 rs2014300 was associated with risk of ESCC assuming codominant [AG/GG, 0.63(0.41–0.97), P:0.018], dominant [AG + AA/GG, 0.59 (0.39–0.89), P:0.010] and log-additive models [0.61 (0.42–0.87), P: 0.005]. Meta-analysis found significant associations between rs2274223 and ESCC under all analyzed genetic models. However, meta-analysis stratified by ethnicity showed a significant association in Asians but not non-Asian populations. No significant association was found for rs13042395 in meta-analysis. This study provided first evidence for association of GWAS-identified variants with risk of ESCC in an Iranian cohort.


Esophageal cancer Polymorphism Iran GWAS Association Meta-analysis 


Compliance with Ethical Standards

Informed Consent

“Informed consent was obtained from all individual participants included in the study.”

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  1. 1.Women’s Reproductive Health Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Student Research Committee, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Medical Genetics Department, School of MedicineTehran University of Medical SciencesTehranIran
  5. 5.Immunology Research CenterTabriz University of Medical SciencesTabrizIran
  6. 6.Department of Medical Genetics, Faculty of MedicineTabriz University of Medical SciencesTabrizIran

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