Tumor Biology

, Volume 37, Issue 6, pp 7119–7128 | Cite as

The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma

  • Huimin Yang
  • Kaihui Yu
  • Ruoheng Zhang
  • Jiatong Li
  • Xiaomou Wei
  • Yuening Zhang
  • Chengdong Zhang
  • Feifan Xiao
  • Dong Zhao
  • Xuandong Lin
  • Huayu Wu
  • Xiaoli Yang


Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual’s susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities.


Nasopharyngeal carcinoma Polymorphisms HLA-DRB1 Allele Ethnic groups Meta-analysis 



The authors gratefully acknowledge the National Natural Science Foundation of China (grants number: 81060214); the Guangxi Natural Science Foundation (grants number: 2011GXNSFA018175); and the Guangxi scientific research and technology development project (grants number: Guikegong1355005-5-7). We thank Dr. Scott S. Tighe for proofreading the manuscript.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Guo X, Johnson RC, Deng H, Liao J, Guan L, Nelson GW, et al. Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China. Int J Cancer. 2009;124:2942–7.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hildesheim A, Apple RJ, Chen CJ, Wang SS, Cheng YJ, Klitz W, et al. Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan. J Natl Cancer Inst. 2002;94:1780–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Ward MH, Pan WH, Cheng YJ, Li FH, Brinton LA, Chen CJ, et al. Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan. Int J Cancer. 2000;86:603–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Xue WQ, Qin HD, Ruan HL, Shugart YY, Jia WH. Quantitative association of tobacco smoking with the risk of nasopharyngeal carcinoma: a comprehensive meta-analysis of studies conducted between 1979 and 2011. Am J Epidemiol. 2013;178:325–38.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhou X, Cui J, Macias V, Kajdacsy-Balla AA, Ye H, Wang J, et al. The progress on genetic analysis of nasopharyngeal carcinoma. Comp Funct Genomics. 2007;57513.Google Scholar
  6. 6.
    Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell. 2004;5:423–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Maxwell JH, Kumar B, Feng FY, McHugh JB, Cordell KG, Eisbruch A, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32:562–7.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Lu CC, Chen JC, Jin YT, Yang HB, Chan SH, Tsai ST. Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese. Int J Cancer. 2003;103:745–51.CrossRefPubMedGoogle Scholar
  9. 9.
    Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, et al. A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet. 2010;42:599–603.CrossRefPubMedGoogle Scholar
  10. 10.
    Hosomichi K, Shiina T, Tajima A, Inoue I. The impact of next-generation sequencing technologies on HLA research. J Hum Genet. 2015;60:665–73.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhu J, Paul WE. CD4 T cells: fates, functions, and faults. Blood. 2008;112:1557–69.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Klein J, Sato A. The HLA system. Second of two parts. N Engl J Med. 2000;343:782–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Hemler JA, Phillips EJ, Mallal SA, Kendall PL. The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy. Ann Allergy Asthma Immunol. 2015;115:471–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Wei LZ, Wang HL, Liu X, Lu YP, Xu F, Yuan JQ, et al. Meta-analysis on the relationship between HLA-DRBl gene polymorphism and cervical cancer in Chinese population. PLoS One. 2014;9, e88439.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gokhale P, Kerkar S, Tongaonkar H, Chaudhari H, Warke H, Salvi V, et al. Variations in immunogenetics, human papillomavirus (HPV) infection & predisposition to cervical cancer in Indian women. Indian J Med Res. 2014;140(Suppl):S36–43.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Safaeian M, Johnson LG, Yu K, Wang SS, Gravitt PE, Hansen JA, et al. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma. Frontiers in Oncology. 2014;4:119.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, et al. Association between HLA-DRB1 alleles polymorphism and hepatocellular carcinoma: a meta-analysis. BMC Gastroenterol. 2010;10:145.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jin YJ, Shim JH, Chung YH, Kim JA, Choi JG, Park WH, et al. Relationship of HLA-DRB1 alleles with hepatocellular carcinoma development in chronic hepatitis B patients. J Clin Gastroenterol. 2012;46:420–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Yan ZH, Fan Y, Wang XH, Mao Q, Deng GH, Wang YM. Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: a meta-analysis. World J Gastroenterol. 2012;18:3119–28.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Jiang DK, Ma XP, Wu X, Peng L, Yin J, Dan Y, et al. Genetic variations in STAT4, C2, HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis. Sci Rep. 2015;5:16278.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Yang M, Kuang X, Li J, Pan Y, Tan M, Lu B, et al. Meta-analysis of the association of HLA-DRB1 with rheumatoid arthritis in Chinese populations. BMC Musculoskelet Disord. 2013;14:307.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Yan L, Wang JM, Zeng K. Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis. Br J Dermatol. 2012;167:768–77.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Khan SW, Iftikhar N, Ahmed TA, Bashir M. HLA-DR alleles in Pakistani patients of pemphigus vulgaris. J Coll Physicians Surg Pak. 2015;25:233–6.PubMedGoogle Scholar
  24. 24.
    Tong X, Chen L, Liu S, Yan Z, Peng S, Zhang Y, et al. Polymorphisms in HLA-DRB1 gene and the risk of tuberculosis: a meta-analysis of 31 studies. Lung. 2015;193:309–18.CrossRefPubMedGoogle Scholar
  25. 25.
    Li CP, Zhou Y, Xiang X, Zhou Y, He M. Relationship of HLA-DRB1 gene polymorphism with susceptibility to pulmonary tuberculosis: updated meta-analysis. Int J Tuberc Lung Dis. 2015;19:841–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang Y, Li M, Xiao F, Teng R, Zhang C, Lan A, et al. Impact of partial daz1/2 deletion and partial daz3/4 deletion on male infertility. Gene. 2015;571:9–16.CrossRefPubMedGoogle Scholar
  27. 27.
    Makni H, Daoud J, Ben Salah H, Mahfoudh N, Haddar O, Karray H, et al. HLA association with nasopharyngeal carcinoma in southern Tunisia. Mol Biol Rep. 2010;37:2533–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Karanikiotis C, Daniilidis M, Karyotis N, Bakogiannis C, Economopoulos T, Murray S, et al. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in Greek patients with nasopharyngeal carcinoma. Strahlenther Onkol. 2008;184:325–31.CrossRefPubMedGoogle Scholar
  29. 29.
    Zeng X, Xiao LL, Li J, Lu JX, Wang XN. Correlation of the polymorphism of HLA-a, b and DRB1 alleles with nasopharyngeal carcinoma in the South of China. Chinese Journal of Cellular and Molecular Immunology 2007:819-820+823Google Scholar
  30. 30.
    Mokni-Baizig N, Ayed K, Ayed FB, Ayed S, Sassi F, Ladgham A, et al. Association between HLA-a/-b antigens and -DRB1 alleles and nasopharyngeal carcinoma in Tunisia. Oncology. 2001;61:55–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Wang R, Hu Y, Yindom LM, Huang L, Wu R, Wang D, et al. Association analysis between HLA-a, -b, -c, -DRB1, and -DQB1 with nasopharyngeal carcinoma among a Han population in northwestern China. Hum Immunol. 2014;75:197–202.CrossRefPubMedGoogle Scholar
  32. 32.
    Burt RD, Vaughan TL, McKnight B, Davis S, Beckmann AM, Smith AG, et al. Associations between human leukocyte antigen type and nasopharyngeal carcinoma in Caucasians in the United States. Cancer Epidemiol Biomarkers Prev. 1996;5:879–87.PubMedGoogle Scholar
  33. 33.
    Wang ZP, Guo SS, Ping Y. The correlation between hla- drb1 allelic polymorphisms and nasopharyngeal carcinoma in Han people in Hunan Province. Practical Preventive Medicine. 2003;129–131.Google Scholar
  34. 34.
    Zeng FF, Liu YT, Lin XL, Fan YY, Zhang XL, Xu CH, et al. Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study. Br J Nutr. 2015;1–8.Google Scholar
  35. 35.
    Pajares S, Arias A, Garcia-Villoria J, Macias-Vidal J, Ros E, de Las HJ, et al. Cholestane-3beta,5alpha,6beta-triol: high levels in Niemann-pick type c, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency. J Lipid Res. 2015;56:1926–35.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Nuttall JR, Supasai S, Kha J, Vaeth BM, Mackenzie GG, Adamo AM, et al. Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway. J Nutr Biochem. 2015;26:1116–23.CrossRefPubMedGoogle Scholar
  37. 37.
    Shen GP, Xu FH, He F, Ruan HL, Cui C, Chen LZ, et al. Pretreatment lifestyle behaviors as survival predictors for patients with nasopharyngeal carcinoma. PLoS One. 2012;7, e36515.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Liu YT, Fan YY, Xu CH, Lin XL, Lu YK, Zhang XL, et al. Habitual consumption of soy products and risk of nasopharyngeal carcinoma in Chinese adults: a case-control study. PLoS One. 2013;8, e77822.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Huimin Yang
    • 1
    • 2
  • Kaihui Yu
    • 3
  • Ruoheng Zhang
    • 1
  • Jiatong Li
    • 1
  • Xiaomou Wei
    • 4
  • Yuening Zhang
    • 1
  • Chengdong Zhang
    • 5
  • Feifan Xiao
    • 1
  • Dong Zhao
    • 1
  • Xuandong Lin
    • 1
  • Huayu Wu
    • 6
  • Xiaoli Yang
    • 1
  1. 1.Medical Scientific Research CenterGuangxi Medical UniversityNanningChina
  2. 2.Shanghai Biomedical LaboratoryShanghaiChina
  3. 3.Department of Pathophysiology, School of Preclinical SciencesGuangxi Medical UniversityNanningChina
  4. 4.Clinical LaboratoryGuangxi Liuzhou Worker’s HospitalLiuzhouChina
  5. 5.Department of Clinical Oncology, Taihe HospitalHubei University of MedicineShiyanChina
  6. 6.Department of Cell Biology and Genetics, School of Premedical SciencesGuangxi Medical UniversityNanningChina

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