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Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck

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An Erratum to this article was published on 09 June 2016

Abstract

Purpose

There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer.

Methods

We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls.

Results

We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control.

Conclusions

The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls.

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References

  1. Jablonska S, Dabrowski J, Jakubowicz K (1972) Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res 32:583–589

    CAS  PubMed  Google Scholar 

  2. Jablonska S, Majewski S (1994) Epidermodysplasia verruciformis: immunological and clinical aspects. Curr Top Microbiol Immunol 186:157–175

    CAS  PubMed  Google Scholar 

  3. Majewski S, Jablonska S, Orth G (1997) Epidermodysplasia verruciformis. Immunological and nonimmunological surveillance mechanisms: role in tumor progression. Clin Dermatol 15:321–334

    Article  CAS  PubMed  Google Scholar 

  4. Majewski S, Malejczyk J, Jablonska S et al (1990) Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis. J Am Acad Dermatol 22:423–427

    Article  CAS  PubMed  Google Scholar 

  5. Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M (2008) Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med 205:35–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M (2002) Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet 32:579–581

    Article  CAS  PubMed  Google Scholar 

  7. Patel AS, Karagas MR, Pawlita M, Waterboer T, Nelson HH (2008) Cutaneous human papillomavirus infection, the EVER2 gene and incidence of squamous cell carcinoma: a case–control study. Int J Cancer 122:2377–2379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Castro FA, Ivansson EL, Schmitt M et al (2012) Contribution of TMC6 and TMC8 (EVER1 and EVER2) variants to cervical cancer susceptibility. Int J Cancer 130:349–355

    Article  CAS  PubMed  Google Scholar 

  9. Stanley MA, Pett MR, Coleman N (2007) HPV: from infection to cancer. Biochem Soc Trans 35:1456–1460

    Article  CAS  PubMed  Google Scholar 

  10. Wang SS, Gonzalez P, Yu K et al (2010) Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS One 5:e8667

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kendall BJ, Macdonald GA, Hayward NK et al (2008) Leptin and the risk of Barrett’s oesophagus. Gut 57:448–454

    Article  CAS  PubMed  Google Scholar 

  12. Antonsson A, Neale RE, Boros S et al (2015) Human papillomavirus status and p16(INK4A) expression in patients with mucosal squamous cell carcinoma of the head and neck in Queensland, Australia. Cancer Epidemiol 39:174–181

    Article  PubMed  Google Scholar 

  13. Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protoc Hum Genet, Chapter 2. doi:10.1002/0471142905.hg0212s60

  14. Levine DM, Ek WE, Zhang R et al (2013) A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus. Nat Genet 45:1487–1493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gardner MJ, Altman DG (1989) Statistics with confidence—confidence intervals and statistical guidelines. British Medical Journal, London

    Google Scholar 

  16. Team RDC (2011) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  17. Hong AM, Grulich AE, Jones D et al (2010) Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets. Vaccine 28:3269–3272

    Article  CAS  PubMed  Google Scholar 

  18. D’Souza G, Kreimer AR, Viscidi R et al (2007) Case–control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944–1956

    Article  PubMed  Google Scholar 

  19. Hocking JS, Stein A, Conway EL et al (2011) Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. Br J Cancer 104:886–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liang C, Kelsey KT, McClean MD et al (2015) A coding variant in TMC8 (EVER2) is associated with high risk HPV infection and head and neck cancer risk. PLoS One 10:e0123716

    Article  PubMed  PubMed Central  Google Scholar 

  21. Horn H, Pott C, Kalla J et al (2010) A multiplex MALDI-TOF MS approach facilitates genotyping of DNA from formalin-fixed paraffin-embedded tumour specimens. Pharmacogenet Genomics 20:598–604

    Article  CAS  PubMed  Google Scholar 

  22. Genomes Project C, Abecasis GR, Altshuler D et al (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061–1073

    Article  Google Scholar 

  23. Kent WJ, Sugnet CW, Furey TS et al (2002) The human genome browser at UCSC. Genome Res 12:996–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pruitt KD, Tatusova T, Maglott DR (2005) NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 33:D501–D504

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Chris Hill, Catherine Bartlett, and Shauna French for help with collection of clinical and lifestyle data. This project was funded by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (APP1006480). The project was supported in part by Award Number R01CA136725 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. This project was conducted in collaboration with the Queensland Head and Neck Cancer Centre. A.A., R.E.N. and D.C.W. are supported by Research Fellowships from the National Health and Medical Research Council of Australia. A.A. was funded by a Research Fellowship from the Garnett Passe and Rodney Williams Memorial Foundation. The funding bodies played no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding bodies.

Author information

Authors and Affiliations

  1. Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia

    Annika Antonsson, Rachel E. Neale & David C. Whiteman

  2. Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Matthew H. Law

  3. Princess Alexandra Hospital, Brisbane, QLD, Australia

    William B. Coman, David I. Pryor & Sandro V. Porceddu

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  1. Annika Antonsson
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  2. Matthew H. Law
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  3. Rachel E. Neale
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  4. William B. Coman
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  6. Sandro V. Porceddu
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  7. David C. Whiteman
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Study of Digestive Health (SDH)

Corresponding author

Correspondence to Annika Antonsson.

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Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

See “Appendix” section for “Study of Digestive Health (SDH)” Members.

Electronic supplementary material

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Supplementary material 1 (DOCX 23 kb)

Appendix: Study of Digestive Health

Appendix: Study of Digestive Health

Controls were derived from the Study of Digestive Health group (SDH). The SDH was supported by Grant Number 5 RO1 CA 001833-02 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. We gratefully acknowledge the cooperation of the following institutions: Sullivan and Nicolaides Pathology (Brisbane); Queensland Medical Laboratory (Brisbane); Queensland Health Pathology Services (Brisbane); Institute of Medical and Veterinary Science (Adelaide); SouthPath (Adelaide). We also acknowledge the contribution of the study nurses and research assistants and would like to thank all of the people who participated in the study. D.C.W. was supported by an NHMRC Research Fellowship (APP1058522).

The SDH Study Group

Study of Digestive Health (SDH) Team

Chief Investigators

David Whiteman, Adele Green, Nicholas Hayward, Peter Parsons, Sandra Pavey, David Purdie, Penny Webb (Queensland Institute of Medical Research); David Gotley, Mark Smithers (University of Queensland/Princess Alexandra Hospital); Paul Drew, Glyn Jamieson (University of Adelaide)

Paul Drew, David Watson (Flinders University of South Australia); Andrew Clouston (Mayne Pathology)

Research Staff D Nancarrow, D Hussey, E Smith, G Mayne

Project Manager S O’Brien (QIMR)

Data Manager T Sadkowsky (QIMR)

Research Nurses

QLD—A. McMurtrie, L. Terry, M. Connard, L. Jackman, S. Perry, M. Davis; SA—D. Roffe, M. Martin, L. Smith

Clinical Collaborators

QLD—A. Clouston (Envoi Pathology), I. Brown (S&N Pathology), N. Walker (QML Pathology); SA—Justin Bessell (Flinders Medical Centre), William Tam (Royal Adelaide Hospital), Andrew Ruskowicz (Institute of Medical and Veterinary Science).

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Antonsson, A., Law, M.H., Neale, R.E. et al. Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck. Cancer Causes Control 27, 809–815 (2016). https://doi.org/10.1007/s10552-016-0749-y

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  • DOI: https://doi.org/10.1007/s10552-016-0749-y

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