Skip to main content

Advertisement

SpringerLink
Log in

The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma

  • Review
  • Published:
Tumor Biology

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

  6. Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell. 2004;5:423–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhu J, Paul WE. CD4 T cells: fates, functions, and faults. Blood. 2008;112:1557–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Klein J, Sato A. The HLA system. Second of two parts. N Engl J Med. 2000;343:782–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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+823

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

  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.

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

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.

Author information

Author notes

    Authors and Affiliations

    1. Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, China

      Huimin Yang, Ruoheng Zhang, Jiatong Li, Yuening Zhang, Feifan Xiao, Dong Zhao, Xuandong Lin & Xiaoli Yang

    2. Shanghai Biomedical Laboratory, Shanghai, 200436, China

      Huimin Yang

    3. Department of Pathophysiology, School of Preclinical Sciences, Guangxi Medical University, Nanning, 530021, China

      Kaihui Yu

    4. Clinical Laboratory, Guangxi Liuzhou Worker’s Hospital, Liuzhou, Guangxi, 545005, China

      Xiaomou Wei

    5. Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442001, China

      Chengdong Zhang

    6. Department of Cell Biology and Genetics, School of Premedical Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, China

      Huayu Wu

    Authors
    1. Huimin Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Kaihui Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ruoheng Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jiatong Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiaomou Wei
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Yuening Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Chengdong Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Feifan Xiao
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Dong Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Xuandong Lin
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Huayu Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Xiaoli Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Huayu Wu or Xiaoli Yang.

    Ethics declarations

    Conflicts of interest

    None

    Additional information

    Huimin Yang, Kaihui Yu, Ruoheng Zhang, Jiatong Li and Xiaomou Wei contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Yang, H., Yu, K., Zhang, R. et al. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma. Tumor Biol. 37, 7119–7128 (2016). https://doi.org/10.1007/s13277-016-5051-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-016-5051-9

    Keywords

    Search

    Navigation