Skip to main content

Advertisement

SpringerLink
Log in

A novel causal model for nasopharyngeal carcinoma

  • Brief report
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

The development of nasopharyngeal carcinoma (NPC) and its unique geographic distribution have long been attributed to a combination of dietary intake of salt-preserved fish, inherited susceptibility, and early-life infection with the Epstein-Barr virus (EBV). New findings from our large, rigorously designed, population-based case–control study of NPC in southern China have enabled substantial revision of this causal model. Here, we briefly summarize these results and provide an updated model of the etiology of NPC. Our new research identifies two EBV genetic variants that may be causally involved in the majority of NPC in southern China, and suggests the rise of modern environmental co-factors accompanying cultural and economic transformation in NPC-endemic regions. These discoveries can be translated directly into clinical and public health advances, including improvement of indoor air quality and oral health, development of an EBV vaccine, enhanced screening strategies, and improved risk prediction. Greater understanding of the roles of environmental, genetic, and viral risk factors can reveal the extent to which these agents act independently or jointly on NPC development. The history of NPC research demonstrates how epidemiology can shed light on the interplay of genes, environment, and infections in carcinogenesis, and how this knowledge can be harnessed for cancer prevention and control.

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

Data availability

Enquiries about data availability should be directed to the authors.

Notes

  1. Keratinizing squamous cell NPC, the histological type that prevails in low-risk populations and usually lacks EBV in tumor cells, quite clearly develops through other pathways [30, 31].

References

  1. Yu MC, Henderson BE (1996) Nasopharyngeal cancer. In: Second Ed, Schottenfeld D, Fraumeni JF (eds) Cancer Epidemiology and Prevention. Oxford University Press, New York, pp 603–618

    Google Scholar 

  2. De-Thé, G, Y. Ito (1978) Nasopharyngeal Carcinoma: Etiology and Control. Proceedings of an International Symposium jointly supported by IARC, the National Cancer Institute (USA) and the Japan Society for the Promotion of Science. Kyoto, Japan, 1977. IARC Scientific Publications, France

  3. Ho HC (1972) Current knowledge of the epidemiology of nasopharyngeal carcinoma-a review, in Oncogenesis and Herpesviruses. Proceedings of a Symposium held at Christ's College, Cambridge, England, 1971. P.M. Biggs, G. de-Thé, and L.N. Payne, Editors. 1972, International Agency for Research on Cancer (IARC): Lyon, France

  4. Chang ET, Adami HO (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15(10):1765–1777

    Article  CAS  PubMed  Google Scholar 

  5. Chan AT, Teo PM, Huang DP (2004) Pathogenesis and treatment of nasopharyngeal carcinoma. Semin Oncol 31(6):794–801

    Article  PubMed  Google Scholar 

  6. Chang ET et al (2021) The evolving epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 30:1035–1047

    Article  CAS  PubMed  Google Scholar 

  7. Ye W et al (2017) Development of a population-based cancer case-control study in southern china. Oncotarget 8(50):87073–87085

    Article  PubMed  PubMed Central  Google Scholar 

  8. Xu M et al (2019) Genome sequencing analysis identifies Epstein-Barr virus subtypes associated with high risk of nasopharyngeal carcinoma. Nat Genet 51(7):1131–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chang ET et al (2017) Active and passive smoking and risk of nasopharyngeal carcinoma: a population-based case-control study in Southern China. Am J Epidemiol 185(12):1272–1280

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen Y et al (2021) Residence characteristics and risk of nasopharyngeal carcinoma in southern China: a population-based case-control study. Environ Int 151:106455

    Article  PubMed  Google Scholar 

  11. Barrett D et al (2019) Past and recent salted fish and preserved food intakes are weakly associated with nasopharyngeal carcinoma risk in adults in Southern China. J Nutr 149(9):1596–1605

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huang TT et al (2021) Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China. Am J Clin Nutr 114(2):462–471

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu Z et al (2016) Oral hygiene and risk of nasopharyngeal carcinoma-a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 25(8):1201–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Debelius JW et al (2021) Subspecies niche specialization in the oral microbiome is associated with nasopharyngeal carcinoma risk. mSystems. https://doi.org/10.1128/mSystems.00065-20

    Article  Google Scholar 

  15. Xiao X et al (2018) Medical history, medication use, and risk of nasopharyngeal carcinoma. Am J Epidemiol 187(10):2117–2125

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen YF et al (2021) Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: a population-based case-control study. Cancer 127(15):2724–2735

    Article  CAS  PubMed  Google Scholar 

  17. Feng R et al (2020) Intake of alcohol and tea and risk of nasopharyngeal carcinoma: a population- based case-control study in southern China. Cancer Epidemiol Biomarkers Prev 30(3):545–553

    Article  PubMed  Google Scholar 

  18. Lin C et al (2019) Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: a population-based case-control study. Cancer 125(24):4462–4470

    Article  PubMed  Google Scholar 

  19. Feng R et al (2019) Body mass index, body shape, and risk of nasopharyngeal carcinoma: a population-based case-control study in Southern China. Cancer Med 8(4):1835–1844

    Article  PubMed  PubMed Central  Google Scholar 

  20. Feng RM et al (2019) Reproductive history and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China. Oral Oncol 88:102–108

    Article  PubMed  Google Scholar 

  21. Yu MC et al (1986) Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong. Cancer Res 46(2):956–961

    CAS  PubMed  Google Scholar 

  22. Yu MC, Huang TB, Henderson BE (1989) Diet and nasopharyngeal carcinoma: a case-control study in Guangzhou. China Int J Cancer 43(6):1077–1082

    Article  CAS  PubMed  Google Scholar 

  23. Yu MC et al (1988) Preserved foods and nasopharyngeal carcinoma: a case-control study in Guangxi. China Cancer Res 48(7):1954–1959

    CAS  PubMed  Google Scholar 

  24. Long M et al (2017) Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies. BMJ Open 7(10):e016582

    Article  PubMed  PubMed Central  Google Scholar 

  25. Xue WQ et al (2013) 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 178(3):325–338

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tse KP et al (2009) Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3. Am J Hum Genet 85(2):194–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bei JX et al (2010) A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet 42(7):599–603

    Article  CAS  PubMed  Google Scholar 

  28. Tang M et al (2012) The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove. PLoS Genet 8(11):e1003103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chin YM et al (2015) HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese. Int J Cancer 136(3):678–687

    CAS  PubMed  Google Scholar 

  30. Chan JKC et al (2005) Nasopharyngeal carcinoma World Health Organization Classification of Tumours. In: Barnes L et al (eds) Pathology & Genetics Head and Neck Tumours. International Agency for Research on Cancer (IARC), Lyon

    Google Scholar 

  31. Vaughan TL et al (1996) Nasopharyngeal cancer in a low-risk population: defining risk factors by histological type. Cancer Epidemiol Biomarkers Prev 5(8):587–593

    CAS  PubMed  Google Scholar 

  32. Wei KR et al (2010) Epidemiological trends of nasopharyngeal carcinoma in China. Asian Pac J Cancer Prev 11(1):29–32

    PubMed  Google Scholar 

  33. Jia WH et al (2006) Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983-2002) in Sihui and Cangwu counties in southern China. BMC Cancer 6:178

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tse LA et al (2006) Incidence rate trends of histological subtypes of nasopharyngeal carcinoma in Hong Kong. Br J Cancer 95(9):1269–1273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bray, F., et al., eds. Cancer Incidence in Five Continents, Vol. XI (electronic version). Lyon: International Agency for Research on Cancer. Available: https://ci5.iarc.fr. Accessed: 15 October 2020. 2017.

  36. Liu Z et al (2020) Patterns of human leukocyte antigen class I and class II associations and cancer. Cancer Res 81:1148–1152

    PubMed  Google Scholar 

  37. Wang TM et al (2018) Fine-mapping of HLA class I and class II genes identified two independent novel variants associated with nasopharyngeal carcinoma susceptibility. Cancer Med 7(12):6308–6316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lam WKJ et al (2020) Sequencing analysis of plasma Epstein-Barr virus DNA reveals nasopharyngeal carcinoma-associated single nucleotide variant profiles. Clin Chem 66(4):598–605

    Article  PubMed  Google Scholar 

  39. World Health Organization, Household air pollution and health. Available: https://www.who.int/news-room/fact-sheets/detail/household-air-pollution-and-health. Updated: 18 May 2018. 2018.

  40. Watt RG (2005) Strategies and approaches in oral disease prevention and health promotion. Bull World Health Organ 83(9):711–718

    PubMed  PubMed Central  Google Scholar 

  41. Rühl J, Leung CS, Munz C (2020) Vaccination against the Epstein-Barr virus. Cell Mol Life Sci 77(21):4315–4324

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Ji MF et al (2019) Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China. Ann Oncol 30(10):1630–1637

    Article  CAS  PubMed  Google Scholar 

  43. Liu Z et al (2013) Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in Southern China. Am J Epidemiol 177(3):242–250

    Article  PubMed  Google Scholar 

  44. Chan KCA et al (2017) Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med 377(6):513–522

    Article  CAS  PubMed  Google Scholar 

  45. Chan KC et al (2013) Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program. Cancer 119(10):1838–1844

    Article  CAS  PubMed  Google Scholar 

  46. Zhang SQ et al (2021) Research status and prospects of biomarkers for nasopharyngeal carcinoma in the era of highthroughput omics (Review). Int J Oncol 58(4):1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Xiao Z, Chen Z (2019) Deciphering nasopharyngeal carcinoma pathogenesis via proteomics. Expert Rev Proteomics 16(6):475–485

    Article  CAS  PubMed  Google Scholar 

  48. Cui Q et al (2017) Nasopharyngeal carcinoma risk prediction via salivary detection of host and Epstein-Barr virus genetic variants. Oncotarget 8(56):95066–95074

    Article  PubMed  Google Scholar 

  49. Lee MH et al (2020) Epstein-Barr virus (EBV) based nasopharyngeal carcinoma (NPC) risk prediction scores are elevated in NPC multiplex family members compared to the general population in Taiwan. J Infect Dis 223:441–443

    Article  PubMed Central  Google Scholar 

  50. Coghill AE et al (2018) Identification of a novel, EBV-based antibody risk stratification signature for early detection of nasopharyngeal carcinoma in Taiwan. Clin Cancer Res 24(6):1305–1314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chen H et al (2017) Multiparametric detection of antibodies against different EBV antigens to predict risk for nasopharyngeal carcinoma in a high-risk population of China. Cancer Prev Res (Phila) 10(9):542–550

    Article  CAS  Google Scholar 

  52. Chen Y et al (2018) Lack of association between cigarette smoking and Epstein Barr virus reactivation in the nasopharynx in people with elevated EBV IgA antibody titres. BMC Cancer 18(1):190

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. He YQ et al (2018) The relationship between environmental factors and the profile of Epstein-Barr virus antibodies in the lytic and latent infection periods in healthy populations from endemic and non-endemic nasopharyngeal carcinoma areas in China. EBioMedicine 30:184–191

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ng CC et al (2009) A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. J Hum Genet 54(7):392–397

    Article  CAS  PubMed  Google Scholar 

  55. Cui Q et al (2016) An extended genome-wide association study identifies novel susceptibility loci for nasopharyngeal carcinoma. Hum Mol Genet 25(16):3626–3634

    Article  CAS  PubMed  Google Scholar 

  56. Ferlay, J., et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. 2013 [cited 2015 July 20]; Available from: http://globocan.iarc.fr.

  57. Edgren G et al (2012) Enigmatic sex disparities in cancer incidence. Eur J Epidemiol 27(3):187–196

    Article  PubMed  Google Scholar 

  58. van Zyl DG, Mautner J, Delecluse HJ (2019) Progress in EBV Vaccines. Front Oncol 9:104

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Financial support for this work was provided by the Sun Yat-sen University Cancer Center.

Author information

Authors and Affiliations

  1. Center for Health Sciences, Exponent Inc, 149 Commonwealth Dr, Menlo Park, CA, 94303, USA

    E. T. Chang

  2. Department of Cancer Prevention Center, Sun Yat-Sen University Cancer Center, Guangzhou, China

    E. T. Chang

  3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    W. Ye & H. O. Adami

  4. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    I. Ernberg

  5. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Y. X. Zeng

  6. Beijing Hospital, Beijing, China

    Y. X. Zeng

  7. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    H. O. Adami

  8. Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway

    H. O. Adami

Authors
  1. E. T. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Ernberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. X. Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. O. Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. T. Chang.

Ethics declarations

Conflict of interest

The author declare no competing interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chang, E.T., Ye, W., Ernberg, I. et al. A novel causal model for nasopharyngeal carcinoma. Cancer Causes Control 33, 1013–1018 (2022). https://doi.org/10.1007/s10552-022-01582-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-022-01582-x

Keywords

Search

Navigation