Skip to main content

Advertisement

SpringerLink
Log in

Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established.

Methods

t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case–control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)+ as compared to t(14;18)− cases.

Results

Among incident FL cases, educational level (χ 2 p = 0.021) and height (χ 2 p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)HF] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)+ FL [OR 6.31 (95 % CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)− cases.

Conclusions

These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status.

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

Similar content being viewed by others

References

  1. Anderson JR, Armitage JO, Weisenburger DD (1998) Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma classification project. Ann Oncol 9:717–720

    Article  CAS  PubMed  Google Scholar 

  2. Jaffe ES (2013) Follicular lymphomas: a tapestry of common and contrasting threads. Haematologica 98:1163–1165

    Article  PubMed Central  PubMed  Google Scholar 

  3. Kridel R, Sehn LH, Gascoyne RD (2012) Pathogenesis of follicular lymphoma. J Clin Invest 122:3424–3431

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Schüler F, Dölken L, Hirt C et al (2009) Prevalence and frequency of circulating t(14;18)-MBR translocation carrying cells in healthy individuals. Int J Cancer 124:958–963

    Article  PubMed Central  PubMed  Google Scholar 

  5. Limpens J, Stad R, Vos C et al (1995) Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood 85:2528–2536

    CAS  PubMed  Google Scholar 

  6. Liu Y, Hernandez AM, Shibata D, Cortopassi GA (1994) BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci USA 91:8910–8914

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Roulland S, Lebailly P, Lecluse Y, Briand M, Pottier D, Gauduchon P (2004) Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides. Cancer Res 64:2264–2269

    Article  CAS  PubMed  Google Scholar 

  8. Roulland S, Kelly RS, Morgado E et al (2014) t(14;18) Translocation: a predictive blood biomarker for follicular lymphoma. J Clin Oncol 32:1347–1355

    Article  PubMed  Google Scholar 

  9. Baccarelli A, Hirt C, Pesatori AC et al (2006) t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy. Carcinogenesis 27:2001–2007

    Article  CAS  PubMed  Google Scholar 

  10. Schroeder JC, Olshan AF, Baric R et al (2001) Agricultural risk factors for t(14;18) subtypes of non-Hodgkin’s lymphoma. Epidemiology 12:701–709

    Article  CAS  PubMed  Google Scholar 

  11. Bentham G, Wolfreys AM, Liu Y et al (1999) Frequencies of hprt–mutations and bcl-2 translocations in circulating human lymphocytes are correlated with United Kingdom sunlight records. Mutagenesis 14:527–532

    Article  CAS  PubMed  Google Scholar 

  12. Schüler F, Hirt C, Dolken G (2003) Chromosomal translocation t(14;18) in healthy individuals. Semin Cancer Biol 13:203–209

    Article  PubMed  Google Scholar 

  13. Bell DA, Liu Y, Cortopassi GA (1995) Occurrence of bcl-2 oncogene translocation with increased frequency in the peripheral blood of heavy smokers. J Natl Cancer Inst 87:223–224

    Article  CAS  PubMed  Google Scholar 

  14. Riboli E, Kaaks R (1997) The EPIC Project: rationale and study design. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 26:S6

    Article  PubMed  Google Scholar 

  15. Riboli E, Hunt K, Slimani N et al (2002) European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5:1113–1124

    Article  CAS  PubMed  Google Scholar 

  16. Roswall N, Freisling H, Bueno-de-Mesquita HB et al (2014) Anthropometric measures and bladder cancer risk: a prospective study in the EPIC cohort. Int J Cancer 135:2918–2929

    Article  CAS  PubMed  Google Scholar 

  17. Slimani N, Kaaks R, Ferrari P et al (2002) European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics. Public Health Nutr 5:1125–1145

    Article  CAS  PubMed  Google Scholar 

  18. Slimani N, Deharveng G, Unwin I et al (2007) The EPIC nutrient database project (ENDB): a first attempt to standardize nutrient databases across the 10 European countries participating in the EPIC study. Eur J Clin Nutr 61:1037–1056

    Article  CAS  PubMed  Google Scholar 

  19. Kaaks R, Riboli E (1997) Validation and calibration of dietary intake measurements in the EPIC project: methodological considerations. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 26:S15

    Article  PubMed  Google Scholar 

  20. Pasqualucci L, Dominguez-Sola D, Chiarenza A et al (2011) Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471:189–195

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Shaknovich R, Melnick A (2011) Epigenetics and B-cell lymphoma. Curr Opin Hematol 18:293–299

    Article  PubMed Central  PubMed  Google Scholar 

  22. Okosun J, Bödör C, Wang J et al (2014) Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet 46:176–181

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Britton JA, Khan AE, Rohrmann S et al (2008) Anthropometric characteristics and non-Hodgkin’s lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Haematologica 93:1666–1677

    Article  PubMed  Google Scholar 

  24. Fisher SG, Fisher RI (2004) The epidemiology of non-Hodgkin’s lymphoma. Oncogene 23:6524–6534

    Article  CAS  PubMed  Google Scholar 

  25. Chang CM, Wang SS, Dave BJ et al (2011) Risk factors for non-Hodgkin lymphoma subtypes defined by histology and t(14;18) in a population-based case–control study. International journal of cancer. J Int du Cancer 129:938–947

    Article  CAS  Google Scholar 

  26. Wadsworth ME, Hardy RJ, Paul AA, Marshall SF, Cole TJ (2002) Leg and trunk length at 43 years in relation to childhood health, diet and family circumstances; evidence from the 1946 national birth cohort. Int J Epidemiol 31:383–390

  27. Vineis P, Miligi L, Crosignani P et al (2000) Delayed infection, family size and malignant lymphomas. J Epidemiol Community Health 54:907–911

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Greaves M (2006) Infection, immune responses and the aetiology of childhood leukaemia. Nat Rev Cancer 6:193–203

    Article  CAS  PubMed  Google Scholar 

  29. Chiu BC-H, Lan Q, Dave BJ, Blair A, Zahm SH, Weisenburger DD (2008) The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma. JNCI Monogr 2008:69–73

    Article  Google Scholar 

  30. Chiu BC, Dave BJ, Blair A et al (2007) Cigarette smoking, familial hematopoietic cancer, hair dye use, and risk of t(14;18)-defined subtypes of non-Hodgkin’s lymphoma. Am J Epidemiol 165:652–659

    Article  PubMed  Google Scholar 

  31. Chiu BC, Dave BJ, Ward MH et al (2008) Dietary factors and risk of t(14;18)-defined subgroups of non-Hodgkin lymphoma. Cancer Causes Control 19:859–867

    Article  PubMed  Google Scholar 

  32. Chiu BC, Dave BJ, Blair A, Gapstur SM, Zahm SH, Weisenburger DD (2006) Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma. Blood 108:1363–1369

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the investigators and participants of the EPIC (European Prospective Investigation into Cancer and Nutrition).

Funding

EPIC study supported by Europe Against Cancer Program of European Commission; Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund of Spanish Ministry of Health; Spanish regional governments of Andalusia, Asturias, Basque, Murcia, and Navarra; Catalan Institute of Oncology; Instituto de Salud Carlos III of Spanish Ministry of Health (Red Temática de Investigación Cooperativa en Cáncer Grant No. DR06/0020); Cancer Research United Kingdom; Medical Research Council United Kingdom; Hellenic Health Foundation; Italian Association for Research on Cancer; Italian National Research Council, Fondazione Istituto Banco Napoli; Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Fund, Dutch Prevention Funds, DutchZorgOnderzoek Nederland, World Cancer Research Fund, and Statistics Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Västerbotten, Sweden; Norwegian Cancer Society; Research Council of Norway; French League Against Cancer; INSERM; Mutuelle Générale del’Education Nationale;3 M(France); Gustave Roussy Institute; and General Councils of France.

Author information

Author notes

    Authors and Affiliations

    1. MRC/PHE Centre for Environment and Health, School of Public Health, Imperial College London, St Mary’s Campus Norfolk Place, London, W2 1PG, UK

      Rachel S. Kelly, Elio Riboli, Marc Gunter, Neil Murphy & Paolo Vineis

    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

      Rachel S. Kelly, Dimitrios Trichopoulos & Pagona Lagiou

    3. Center of Immunology of Marseille-Luminy (CIML), Université de la Méditerranée, Marseille, France

      Sandrine Roulland, Ester Morgado, Stéphanie Sungalee, Nathalie Jouve & Bertrand Nadel

    4. INSERM U631, Marseille, France

      Sandrine Roulland, Ester Morgado, Stéphanie Sungalee, Nathalie Jouve & Bertrand Nadel

    5. CNRS UMR6102, Marseille, France

      Sandrine Roulland, Ester Morgado, Stéphanie Sungalee, Nathalie Jouve & Bertrand Nadel

    6. Cancer Registry and Histopathology Unit, “Civic - M.P.Arezzo” Hospital, ASP Ragusa, Ragusa, Italy

      Rosario Tumino

    7. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

      Vittorio Krogh

    8. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

      Salvatore Panico

    9. HuGeF - Human Genetics Foundation, Turin, Italy

      Silvia Polidoro & Paolo Vineis

    10. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy

      Giovanna Masala

    11. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain

      María-José Sánchez

    12. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

      María-José Sánchez, Maria-Dolores Chirlaque & Aurelio Barricarte Gurrea

    13. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain

      Maria-Dolores Chirlaque

    14. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain

      Núria Sala

    15. Navarre Public Health Institute, Pamplona, Spain

      Aurelio Barricarte Gurrea

    16. Public Health Direction and Ciberesp-Biodonostia Basque Regional Health Department, Vitoria, Spain

      Miren Dorronsoro

    17. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

      Ruth C. Travis

    18. Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands

      Roel Vermeulen

    19. Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

      H. B. Bueno-de-Mesquita

    20. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands

      H. B. Bueno-de-Mesquita

    21. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands

      Petra H. Peeters

    22. Hellenic Health Foundation, 13 Kaisareias Street, 115 27, Athens, Greece

      Antonia Trichopoulou & Dimitrios Trichopoulos

    23. Bureau of Epidemiologic Research, Academy of Athens, 23 Alexandroupoleos Street, 115 27, Athens, Greece

      Antonia Trichopoulou, Dimitrios Trichopoulos & Pagona Lagiou

    24. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, 75 M. Asias Street, Goudi, 115 27, Athens, Greece

      Pagona Lagiou

    25. Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany

      Alexandra Nieters

    26. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

      Federico Canzian & Rudolf Kaaks

    27. Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrüucke, Nuthetal, Germany

      Heiner Boeing

    28. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway

      Elisabete Weiderpass

    29. Cancer Registry of Norway, Oslo, Norway

      Elisabete Weiderpass

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

      Elisabete Weiderpass

    31. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland

      Elisabete Weiderpass

    32. Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden

      Tanja Stocks

    33. Department of Perioperative and Surgical Sciences, Umeå University, Umeå, Sweden

      Tanja Stocks

    34. Department of Radiation Sciences, Head Regional Cancer Center North, Umeå University, Umeå, Sweden

      Beatrice Melin

    35. Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark

      Kim Overvad

    36. Danish Cancer Society Research Center, Copenhagen, Denmark

      Anne Tjønneland & Anja Olsen

    37. International Agency for Research on Cancer (IARC-WHO), 69372, Lyon, France

      Paul Brennan & Mattias Johansson

    Authors
    1. Rachel S. Kelly
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Sandrine Roulland
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ester Morgado
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Stéphanie Sungalee
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Nathalie Jouve
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Rosario Tumino
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Vittorio Krogh
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Salvatore Panico
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Silvia Polidoro
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Giovanna Masala
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. María-José Sánchez
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Maria-Dolores Chirlaque
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Núria Sala
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Aurelio Barricarte Gurrea
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Miren Dorronsoro
      View author publications

      You can also search for this author in PubMed Google Scholar

    16. Ruth C. Travis
      View author publications

      You can also search for this author in PubMed Google Scholar

    17. Elio Riboli
      View author publications

      You can also search for this author in PubMed Google Scholar

    18. Marc Gunter
      View author publications

      You can also search for this author in PubMed Google Scholar

    19. Neil Murphy
      View author publications

      You can also search for this author in PubMed Google Scholar

    20. Roel Vermeulen
      View author publications

      You can also search for this author in PubMed Google Scholar

    21. H. B. Bueno-de-Mesquita
      View author publications

      You can also search for this author in PubMed Google Scholar

    22. Petra H. Peeters
      View author publications

      You can also search for this author in PubMed Google Scholar

    23. Antonia Trichopoulou
      View author publications

      You can also search for this author in PubMed Google Scholar

    24. Dimitrios Trichopoulos
      View author publications

      You can also search for this author in PubMed Google Scholar

    25. Pagona Lagiou
      View author publications

      You can also search for this author in PubMed Google Scholar

    26. Alexandra Nieters
      View author publications

      You can also search for this author in PubMed Google Scholar

    27. Federico Canzian
      View author publications

      You can also search for this author in PubMed Google Scholar

    28. Rudolf Kaaks
      View author publications

      You can also search for this author in PubMed Google Scholar

    29. Heiner Boeing
      View author publications

      You can also search for this author in PubMed Google Scholar

    30. Elisabete Weiderpass
      View author publications

      You can also search for this author in PubMed Google Scholar

    31. Tanja Stocks
      View author publications

      You can also search for this author in PubMed Google Scholar

    32. Beatrice Melin
      View author publications

      You can also search for this author in PubMed Google Scholar

    33. Kim Overvad
      View author publications

      You can also search for this author in PubMed Google Scholar

    34. Anne Tjønneland
      View author publications

      You can also search for this author in PubMed Google Scholar

    35. Anja Olsen
      View author publications

      You can also search for this author in PubMed Google Scholar

    36. Paul Brennan
      View author publications

      You can also search for this author in PubMed Google Scholar

    37. Mattias Johansson
      View author publications

      You can also search for this author in PubMed Google Scholar

    38. Bertrand Nadel
      View author publications

      You can also search for this author in PubMed Google Scholar

    39. Paolo Vineis
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Paolo Vineis.

    Ethics declarations

    Conflicts of interest

    R. Kelly, S. Roulland, P.Vineis, and B. Nadal hold a patent for the t(14;18)HF biomarker (Nadal B, Roulland S, Vineis P, Kelly RS. Methods for Predicting Whether a Subject is at Risk of Developing a Follicular Lymphoma France: 12118, filed December 2013).

    Informed consent

    The study was approved by the committees on research ethics each of the participating centers and conducted in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

    Additional information

    Rachel S. Kelly, Sandrine Roulland, Paolo Vineis and Bertrand Nadel have contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 59 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Kelly, R.S., Roulland, S., Morgado, E. et al. Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma. Cancer Causes Control 26, 1845–1855 (2015). https://doi.org/10.1007/s10552-015-0677-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10552-015-0677-2

    Keywords

    Search

    Navigation