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Cancer Causes & Control

, Volume 26, Issue 12, pp 1845–1855 | Cite as

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

  • Rachel S. Kelly
  • Sandrine Roulland
  • Ester Morgado
  • Stéphanie Sungalee
  • Nathalie Jouve
  • Rosario Tumino
  • Vittorio Krogh
  • Salvatore Panico
  • Silvia Polidoro
  • Giovanna Masala
  • María-José Sánchez
  • Maria-Dolores Chirlaque
  • Núria Sala
  • Aurelio Barricarte Gurrea
  • Miren Dorronsoro
  • Ruth C. Travis
  • Elio Riboli
  • Marc Gunter
  • Neil Murphy
  • Roel Vermeulen
  • H. B. Bueno-de-Mesquita
  • Petra H. Peeters
  • Antonia Trichopoulou
  • Dimitrios Trichopoulos
  • Pagona Lagiou
  • Alexandra Nieters
  • Federico Canzian
  • Rudolf Kaaks
  • Heiner Boeing
  • Elisabete Weiderpass
  • Tanja Stocks
  • Beatrice Melin
  • Kim Overvad
  • Anne Tjønneland
  • Anja Olsen
  • Paul Brennan
  • Mattias Johansson
  • Bertrand Nadel
  • Paolo VineisEmail author
Original paper

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.

Keywords

Follicular lymphoma Translocation t(14;18) Height 

Notes

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.

Compliance with ethical standards

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.

Supplementary material

10552_2015_677_MOESM1_ESM.docx (60 kb)
Supplementary material 1 (DOCX 59 kb)

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Rachel S. Kelly
    • 1
    • 2
  • Sandrine Roulland
    • 3
    • 4
    • 5
  • Ester Morgado
    • 3
    • 4
    • 5
  • Stéphanie Sungalee
    • 3
    • 4
    • 5
  • Nathalie Jouve
    • 3
    • 4
    • 5
  • Rosario Tumino
    • 6
  • Vittorio Krogh
    • 7
  • Salvatore Panico
    • 8
  • Silvia Polidoro
    • 9
  • Giovanna Masala
    • 10
  • María-José Sánchez
    • 11
    • 12
  • Maria-Dolores Chirlaque
    • 12
    • 13
  • Núria Sala
    • 14
  • Aurelio Barricarte Gurrea
    • 12
    • 15
  • Miren Dorronsoro
    • 16
  • Ruth C. Travis
    • 17
  • Elio Riboli
    • 1
  • Marc Gunter
    • 1
  • Neil Murphy
    • 1
  • Roel Vermeulen
    • 18
  • H. B. Bueno-de-Mesquita
    • 19
    • 20
  • Petra H. Peeters
    • 21
  • Antonia Trichopoulou
    • 22
    • 23
  • Dimitrios Trichopoulos
    • 2
    • 22
    • 23
  • Pagona Lagiou
    • 2
    • 23
    • 24
  • Alexandra Nieters
    • 25
  • Federico Canzian
    • 26
  • Rudolf Kaaks
    • 26
  • Heiner Boeing
    • 27
  • Elisabete Weiderpass
    • 28
    • 29
    • 30
    • 31
  • Tanja Stocks
    • 32
    • 33
  • Beatrice Melin
    • 34
  • Kim Overvad
    • 35
  • Anne Tjønneland
    • 36
  • Anja Olsen
    • 36
  • Paul Brennan
    • 37
  • Mattias Johansson
    • 37
  • Bertrand Nadel
    • 3
    • 4
    • 5
  • Paolo Vineis
    • 1
    • 9
    Email author
  1. 1.MRC/PHE Centre for Environment and Health, School of Public HealthImperial College LondonLondonUK
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Center of Immunology of Marseille-Luminy (CIML)Université de la MéditerranéeMarseilleFrance
  4. 4.INSERM U631MarseilleFrance
  5. 5.CNRS UMR6102MarseilleFrance
  6. 6.Cancer Registry and Histopathology Unit, “Civic - M.P.Arezzo” HospitalASP RagusaRagusaItaly
  7. 7.Epidemiology and Prevention UnitFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  8. 8.Department of Clinical and Experimental MedicineFederico II UniversityNaplesItaly
  9. 9.HuGeF - Human Genetics FoundationTurinItaly
  10. 10.Molecular and Nutritional Epidemiology UnitCancer Research and Prevention Institute – ISPOFlorenceItaly
  11. 11.Escuela Andaluza de Salud PúblicaInstituto de Investigación Biosanitaria de Granada (Granada.ibs)GranadaSpain
  12. 12.CIBER de Epidemiología y Salud Pública (CIBERESP)MadridSpain
  13. 13.Department of EpidemiologyMurcia Regional Health AuthorityMurciaSpain
  14. 14.Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research LaboratoryCatalan Institute of Oncology (IDIBELL)BarcelonaSpain
  15. 15.Navarre Public Health InstitutePamplonaSpain
  16. 16.Public Health Direction and Ciberesp-Biodonostia Basque Regional Health DepartmentVitoriaSpain
  17. 17.Cancer Epidemiology Unit, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK
  18. 18.Division of Environmental Epidemiology, Institute for Risk Assessment SciencesUtrecht UniversityUtrechtThe Netherlands
  19. 19.Department for Determinants of Chronic Diseases (DCD)National Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands
  20. 20.Department of Gastroenterology and HepatologyUniversity Medical CentreUtrechtThe Netherlands
  21. 21.Department of Epidemiology, Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  22. 22.Hellenic Health FoundationAthensGreece
  23. 23.Bureau of Epidemiologic ResearchAcademy of AthensAthensGreece
  24. 24.Department of Hygiene, Epidemiology and Medical StatisticsUniversity of Athens Medical SchoolAthensGreece
  25. 25.Center for Chronic ImmunodeficiencyUniversity Medical Center FreiburgFreiburgGermany
  26. 26.Genomic Epidemiology GroupGerman Cancer Research Center (DKFZ)HeidelbergGermany
  27. 27.Department of EpidemiologyGerman Institute of Human Nutrition (DIfE)NuthetalGermany
  28. 28.Department of Community Medicine, Faculty of Health SciencesUniversity of Tromsø, The Arctic University of NorwayTromsøNorway
  29. 29.Cancer Registry of NorwayOsloNorway
  30. 30.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  31. 31.Department of Genetic EpidemiologyFolkhälsan Research CenterHelsinkiFinland
  32. 32.Department of Clinical Sciences in MalmöLund UniversityLundSweden
  33. 33.Department of Perioperative and Surgical SciencesUmeå UniversityUmeåSweden
  34. 34.Department of Radiation Sciences, Head Regional Cancer Center NorthUmeå UniversityUmeåSweden
  35. 35.Section for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
  36. 36.Danish Cancer Society Research CenterCopenhagenDenmark
  37. 37.International Agency for Research on Cancer (IARC-WHO)LyonFrance

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