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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
  • 13 Downloads

Abstract

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.

Keywords

Esophageal cancer Polymorphism Iran GWAS Association Meta-analysis 

Notes

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.

References

  1. 1.
    Schweigert M, Dubecz A, Stein HJ (2013) Oesophageal cancer--an overview. Nat Rev Gastroenterol Hepatol 10(4):230–244.  https://doi.org/10.1038/nrgastro.2012.236 CrossRefGoogle Scholar
  2. 2.
    Castro C, Bosetti C, Malvezzi M, Bertuccio P, Levi F, Negri E, La Vecchia C, Lunet N (2014) Patterns and trends in esophageal cancer mortality and incidence in Europe (1980-2011) and predictions to 2015. Ann Oncol 25(1):283–290.  https://doi.org/10.1093/annonc/mdt486 CrossRefGoogle Scholar
  3. 3.
    Mahboubi E, Kmet J, Cook PJ, Day NE, Ghadirian P, Salmasizadeh S (1973) Oesophageal cancer studies in the Caspian Littoral of Iran: the Caspian cancer registry. Br J Cancer 28(3):197–214CrossRefGoogle Scholar
  4. 4.
    Zare M, Jazii FR, Alivand MR, Nasseri NK, Malekzadeh R, Yazdanbod M (2009) Qualitative analysis of adenomatous polyposis coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker. BMC Cancer 9(1):24.  https://doi.org/10.1186/1471-2407-9-24 CrossRefGoogle Scholar
  5. 5.
    Sadjadi A, Marjani H, Semnani S, Nasseri-Moghaddam S (2010) Esophageal Cancer in Iran: a review. Middle East J Cancer 1(1)Google Scholar
  6. 6.
    Mosavi-Jarrahi A, Mohagheghi MA (2006) Epidemiology of esophageal cancer in the high-risk population of Iran. Asian Pac J Cancer Prev 7(3):375–380Google Scholar
  7. 7.
    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(7):679–684.  https://doi.org/10.1038/ng.849 CrossRefGoogle Scholar
  8. 8.
    Nariman-Saleh-Fam Z, Bastami M, Somi MH, Samadi N, Abbaszadegan MR, Behjati F, Ghaedi H, Tavakkoly-Bazzaz J, Masotti A (2016) In silico dissection of miRNA targetome polymorphisms and their role in regulating miRNA-mediated gene expression in esophageal cancer. Cell Biochem Biophys 74:1–15.  https://doi.org/10.1007/s12013-016-0754-5 CrossRefGoogle Scholar
  9. 9.
    Saadatian Z, Masotti A, Nariman Saleh Fam Z, Alipoor B, Bastami M, Ghaedi H (2014) Single-nucleotide polymorphisms within MicroRNAs sequences and their 3' UTR target sites may regulate gene expression in gastrointestinal tract cancers. Iran Red Crescent Med J 16(7):e16659.  https://doi.org/10.5812/ircmj.16659 CrossRefGoogle Scholar
  10. 10.
    Bastami M, Nariman-Saleh-Fam Z, Saadatian Z, Nariman-Saleh-Fam L, Omrani MD, Ghaderian SM, Masotti A (2016) The miRNA targetome of coronary artery disease is perturbed by functional polymorphisms identified and prioritized by in-depth bioinformatics analyses exploiting genome-wide association studies. Gene 594(1):74–81.  https://doi.org/10.1016/j.gene.2016.08.054 CrossRefGoogle Scholar
  11. 11.
    Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M, Tanaka H (2013) Epidemiology of esophageal cancer in Japan and China. J Epidemiol 23(4):233–242CrossRefGoogle Scholar
  12. 12.
    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, 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(9):764–767.  https://doi.org/10.1038/ng.649 CrossRefGoogle Scholar
  13. 13.
    Wu C, Wang Z, Song X, Feng XS, Abnet CC (2014) Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nat Genet 46(9):1001–1006.  https://doi.org/10.1038/ng.3064 CrossRefGoogle Scholar
  14. 14.
    Wang LD, Zhou FY, Li XM et al (2010) Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet 42(9):759–763.  https://doi.org/10.1038/ng.648
  15. 15.
    Gu H, Ding G, Zhang W, Liu C, Chen Y, Chen S, Jiang P (2012) Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population. Mol Biol Rep 39(9):9105–9111.  https://doi.org/10.1007/s11033-012-1782-x CrossRefGoogle Scholar
  16. 16.
    Palmer AJ, Lochhead P, Hold GL, Rabkin CS, Chow WH, Lissowska J, Vaughan TL, Berry S, Gammon M, Risch H, el-Omar EM (2012) Genetic variation in C20orf54, PLCE1 and MUC1 and the risk of upper gastrointestinal cancers in Caucasian populations. Eur J Cancer Prev 21(6):541–544.  https://doi.org/10.1097/CEJ.0b013e3283529b79 CrossRefGoogle Scholar
  17. 17.
    Bye H, Prescott NJ, Lewis CM, Matejcic M, Moodley L, Robertson B, Rensburg C, Parker MI, Mathew CG (2012) Distinct genetic association at the PLCE1 locus with oesophageal squamous cell carcinoma in the south African population. Carcinogenesis 33(11):2155–2161.  https://doi.org/10.1093/carcin/bgs262 CrossRefGoogle Scholar
  18. 18.
    Nariman-Saleh-Fam Z, Bastami M, Somi MH, Behjati F, Mansoori Y, Daraei A, Saadatian Z, Nariman-Saleh-Fam L, Mahmoodzadeh H, Makhdoumi Y, Tabrizi FV, Ebrahimi-Sharif B, Hezarian A, Naghashi S, Abbaszadegan MR, Tavakkoly-Bazzaz J (2017) miRNA-related polymorphisms in miR-423 (rs6505162) and PEX6 (rs1129186) and risk of esophageal squamous cell carcinoma in an Iranian cohort. Genet Test Mol Biomarkers 21(6):382–390.  https://doi.org/10.1089/gtmb.2016.0346 CrossRefGoogle Scholar
  19. 19.
    Umar M, Upadhyay R, Kumar S, Ghoshal UC, Mittal B (2014) Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population. Tumour Biol 35(11):11667–11676.  https://doi.org/10.1007/s13277-014-2458-z CrossRefGoogle Scholar
  20. 20.
    Bastami M, Ghaderian SM, Omrani MD, Mirfakhraie R, Nariman-Saleh-Fam Z, Mansoori Y, Masotti A (2015) Evaluating the association of common UBE2Z variants with coronary artery disease in an Iranian population. Cell Mol Biol (Noisy-le-grand) 61(7):50–54Google Scholar
  21. 21.
    Bastami M, Ghaderian SM, Omrani MD, Mirfakhraie R, Vakili H, Parsa SA, Nariman-Saleh-Fam Z, Masotti A (2016) MiRNA-related polymorphisms in miR-146a and TCF21 are associated with increased susceptibility to coronary artery disease in an Iranian population. Genet Test Mol Biomarkers 20(5):241–248.  https://doi.org/10.1089/gtmb.2015.0253 CrossRefGoogle Scholar
  22. 22.
    Graffelman J (2015) Exploring Diallelic Genetic Markers: The HardyWeinberg Package. 2015 64(3):23.  https://doi.org/10.18637/jss.v064.i03
  23. 23.
    Gonzalez JR, Armengol L, Sole X, Guino E, Mercader JM, Estivill X, Moreno V (2007) SNPassoc: an R package to perform whole genome association studies. Bioinformatics 23(5):644–645.  https://doi.org/10.1093/bioinformatics/btm025 CrossRefGoogle Scholar
  24. 24.
    Schwarzer G (2007) meta: An R package for meta-analysis. R News (3):40–45Google Scholar
  25. 25.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefGoogle Scholar
  26. 26.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748Google Scholar
  27. 27.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101CrossRefGoogle Scholar
  28. 28.
    Malik MA, Umar M, Gupta U, Zargar SA, Mittal B (2014) Phospholipase C epsilon 1 (PLCE1 rs2274223A>G, rs3765524C>T and rs7922612C>T) polymorphisms and esophageal cancer risk in the Kashmir Valley. Asian Pac J Cancer Prev 15(10):4319–4323CrossRefGoogle Scholar
  29. 29.
    Dong Y, Chen J, Chen Z, Tian C, Lu H, Ruan J, Yang W (2015) Evaluating the Association of Eight Polymorphisms with Cancer susceptibility in a Han Chinese population. PLoS One 10(7):e0132797.  https://doi.org/10.1371/journal.pone.0132797 CrossRefGoogle Scholar
  30. 30.
    Dura P, Bregitha CV, te Morsche RH et al (2013) GWAS-uncovered SNPs in PLCE1 and RFT2 genes are not implicated in Dutch esophageal adenocarcinoma and squamous cell carcinoma etiology. Eur J Cancer Prev 22(5):417–419.  https://doi.org/10.1097/CEJ.0b013e32835c7f53 CrossRefGoogle Scholar
  31. 31.
    Piao JM, Shin MH, Kim HN, Song HR, Kweon SS, Choi JS, Shim HJ, Hwang JE, Bae WK, Kim SH, Choi YD, Cui LH (2014) Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population. Dis Esophagus 27(8):798–801.  https://doi.org/10.1111/dote.12155 CrossRefGoogle Scholar
  32. 32.
    Duan F, Xie W, Cui L, Wang P, Song C, Qu H, Wang K, Zhang J, Dai L (2013) Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: based on published genome-wide association studies in a central Chinese population. Cancer Epidemiol 37(5):647–652.  https://doi.org/10.1016/j.canep.2013.04.009 CrossRefGoogle Scholar
  33. 33.
    Hu H, Yang J, Sun Y, Yang Y, Qian J, Jin L, Wang M, Bi R, Zhang R, Zhu M, Sun M, Ma H, Wei Q, Jiang G, Zhou X, Chen H (2012) Putatively functional PLCE1 variants and susceptibility to esophageal squamous cell carcinoma (ESCC): a case-control study in eastern Chinese populations. Ann Surg Oncol 19(7):2403–2410.  https://doi.org/10.1245/s10434-011-2160-y CrossRefGoogle Scholar
  34. 34.
    Yang J, Wu H, Wei S, Xiong H, Fu X, Qi Z, Jiang Q, Li W, Hu G, Yuan X, Liao Z (2014) HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of esophageal squamous cell carcinoma (ESCC). BMC Cancer 14(1).  https://doi.org/10.1186/1471-2407-14-501
  35. 35.
    Zhou RM, Li Y, Wang N, Liu BC, Chen ZF, Zuo LF (2012) PLC-ε1 gene polymorphisms significantly enhance the risk of esophageal squamous cell carcinoma in individuals with a family history of upper gastrointestinal cancers. Arch Med Res 43(7):578–584.  https://doi.org/10.1016/j.arcmed.2012.09.006 CrossRefGoogle Scholar
  36. 36.
    Song X, Zhou FY, Zhang LQ (2012) Correlation of PLCE1 gene polymorphism in the smoker/non-smokers, drinking /non-drinking, and BMI subgroups with esophageal squamous cell carcinoma. J Henan University 31:186–190Google Scholar
  37. 37.
    Chen YZ, Cui XB, Pang XL, Li L, Hu JM, Liu CX, Cao YW, Yang L, Li F (2013) Relationship between rs2274223 and rs3765524 polymorphisms of PLCE1 and risk of esophageal squamous cell carcinoma in a kazakh Chinese population. Chin J Pathol 42(12):795–800.  https://doi.org/10.3760/cma.j.issn.0529-5807.2013.12.002 Google Scholar
  38. 38.
    Wei W, Ji A, Wang J, Wei Z, Lian C, Yang J, Ma L, Ma L, Qin X, Wang LD (2013) Functional single nucleotide polymorphism in C20orf54 modifies susceptibility to esophageal squamous cell carcinoma. Dis Esophagus 26(1):97–103.  https://doi.org/10.1111/j.1442-2050.2012.01339.x CrossRefGoogle Scholar
  39. 39.
    Tan HZ, Wu ZY, Wu JY, Long L, Jiao JW, Peng YH, Xu YW, Li SS, Wang W, Zhang JJ, Li EM, Xu LY (2016) Single nucleotide polymorphism rs13042395 in the SLC52A3 gene as a biomarker for regional lymph node metastasis and relapse-free survival of esophageal squamous cell carcinoma patients. BMC Cancer 16(560):560.  https://doi.org/10.1186/s12885-016-2588-3 CrossRefGoogle Scholar
  40. 40.
    Xue W, Zhu M, Wang Y, He J, Zheng L (2015) Association between PLCE1 rs2274223 a > G polymorphism and cancer risk: proof from a meta-analysis. Sci Rep 5(7986).  https://doi.org/10.1038/srep07986
  41. 41.
    Martins M, McCarthy A, Baxendale R, Guichard S, Magno L, Kessaris N, El-Bahrawy M, Yu P, Katan M (2014) Tumor suppressor role of phospholipase C epsilon in Ras-triggered cancers. Proc Natl Acad Sci U S A 111(11):4239–4244.  https://doi.org/10.1073/pnas.1311500111 CrossRefGoogle Scholar
  42. 42.
    Danielsen SA, Cekaite L, Agesen TH, Sveen A, Nesbakken A, Thiis-Evensen E, Skotheim RI, Lind GE, Lothe RA (2011) Phospholipase C isozymes are deregulated in colorectal cancer--insights gained from gene set enrichment analysis of the transcriptome. PLoS One 6(9):e24419.  https://doi.org/10.1371/journal.pone.0024419 CrossRefGoogle Scholar
  43. 43.
    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(8):1424–1432.  https://doi.org/10.1093/carcin/bgp125 CrossRefGoogle Scholar
  44. 44.
    Zhao L, Wei ZB, Yang CQ, Chen JJ, Li D, Ji AF, Ma L (2014) Effects of PLCE1 gene silencing by RNA interference on cell cycling and apoptosis in esophageal carcinoma cells. Asian Pac J Cancer Prev 15(13):5437–5442CrossRefGoogle Scholar
  45. 45.
    Chen YZ, Cui XB, Hu JM, Zhang WJ, Li SG, Yang L, Shen XH, Liu CX, Pan QF, Yu SY, Yuan XL, Yang L, Gu WY, Chen JZ, Wang LD, Li F (2013) Overexpression of PLCE1 in Kazakh esophageal squamous cell carcinoma: implications in cancer metastasis and aggressiveness. Apmis 121(10):908–918.  https://doi.org/10.1111/apm.12095 CrossRefGoogle Scholar
  46. 46.
    Cui XB, Pang XL, Li S, Jin J, Hu JM, Yang L, Liu CX, Li L, Wen SJ, Liang WH, Chen YZ, Li F (2014) Elevated expression patterns and tight correlation of the PLCE1 and NF-kappaB signaling in Kazakh patients with esophageal carcinoma. Med Oncol 31(1):791.  https://doi.org/10.1007/s12032-013-0791-5 CrossRefGoogle Scholar
  47. 47.
    Li Y, An J, Huang S, Liao H, Weng Y, Cai S, Zhang J (2014) PLCE1 suppresses p53 expression in esophageal cancer cells. Cancer Investig 32(6):236–240.  https://doi.org/10.3109/07357907.2014.905588 CrossRefGoogle Scholar
  48. 48.
    Cui XB, Chen YZ, Pang XL, Liu W, Hu JM, Li SG, Yang L, Zhang WJ, Liu CX, Cao YW, Jiang JF, Gu WY, Pang J, Yang L, Yuan XL, Yu SY, Li F (2013) Multiple polymorphisms within the PLCE1 are associated with esophageal cancer via promoting the gene expression in a Chinese Kazakh population. Gene 530(2):315–322.  https://doi.org/10.1016/j.gene.2013.08.057 CrossRefGoogle Scholar
  49. 49.
    Duan F, Cui S, Song C, Zhao X, Dai L, Shen Y (2015) Esophageal squamous cell carcinoma and gastric cardia adenocarcinoma shared susceptibility locus in C20orf54: evidence from published studies. Sci Rep 5(11961).  https://doi.org/10.1038/srep11961
  50. 50.
    Wu H, Zheng J, Deng J, Zhang L, Li N, Li W, Li F, Lu J, Zhou Y (2015) LincRNA-uc002yug.2 involves in alternative splicing of RUNX1 and serves as a predictor for esophageal cancer and prognosis. Oncogene 34(36):4723–4734.  https://doi.org/10.1038/onc.2014.400 CrossRefGoogle Scholar

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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