Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma
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.
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.
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.
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.
KeywordsFollicular lymphoma Translocation t(14;18) Height
We thank the investigators and participants of the EPIC (European Prospective Investigation into Cancer and Nutrition).
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).
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.
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