t (14; 18) Translocation

PURPOSE: The (14; 18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t (14; 18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t (14; 18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. PARTICIPANTS AND METHODS: Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t (14; 18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t (14; 18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. RESULTS: Clonal analysis of t (14; 18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t (14; 18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t (14; 18) prevalence and frequency than controls (P<. 001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency> 10 (-4)(odds ratio, 23.17; 95% CI, 9.98 to 67.31; P<. 001). Remarkably, risk estimates …