Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma.
Kelly RS., Roulland S., Morgado E., Sungalee S., Jouve N., Tumino R., Krogh V., Panico S., Polidoro S., Masala G., Sánchez MJ., Chirlaque MD., Sala N., Gurrea AB., Dorronsoro M., Travis RC., Riboli E., Gunter M., Murphy N., Vermeulen R., Bueno-de-Mesquita HB., Peeters PH., Trichopoulou A., Trichopoulos D., Lagiou P., Nieters A., Canzian F., Kaaks R., Boeing H., Weiderpass E., Stocks T., Melin B., Overvad K., Tjønneland A., Olsen A., Brennan P., Johansson M., Nadel B., Vineis P.
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.