High t(14;18) Translocation Frequency Predicts Follicular Lymphoma up to 15 Years Later


Key Points

  • High t(14;18) frequency is predictive of follicular lymphoma up to 15 years before diagnosis.
  • Overall, frequency > 1×10-4 is associated with a 23-fold higher risk of follicular lymphoma.

The t(14;18) translocation is a hallmark and critical event in the development of follicular lymphoma, but it is also detectable in otherwise healthy persons, and its relationship to progression to disease is unclear. In a study reported in the Journal of Clinical Oncology, Roulland et al found that the frequency of t(14;18)-positive cells in blood from healthy individuals has predictive power for development of follicular lymphoma for up to 15 years after measurement.

Study Details

In the study, 100 individuals who developed follicular lymphoma at 2 to 161 months after enrollment were identified from among 520,000 healthy participants in the EPIC cohort, which has followed participants for incidence of cancer for > 15 years. Prediagnostic blood from these participants and 218 controls (discovery cohort) matched for age, sex, study center, and time since blood draw were screened for t(14;18) using sensitive polymerase chain reaction–based assays. Results were validated in an independent cohort of 65 case participants and 128 controls.

Higher Prediagnostic Levels in Incident Cases

Clonal analysis of t(14;18) junctions in paired prediagnostic blood vs tumor samples showed that progression to follicular lymphoma occurred from t(14;18)-positive committed precursors.

In the EPIC cohort, the prevalence of t(14;18) was significantly higher in incident follicular lymphoma cases vs controls (56% vs 28.9%, P < .001), as were the mean (97 vs 0.8×10-5, P < .001) and median (0.2 vs 0.1×10-5, P < .001) frequencies of t(14;18) in all samples and the mean (162 vs 2.3×10-5, P <.01) and median (3.8 vs 0.2×10-5, P < .001) frequencies in samples from t(14;18)-positive participants.

Risk Associated With Threshold Level

In the EPIC discovery cohort, unconditional logistic regression showed an approximately 15-fold higher risk of subsequent follicular lymphoma associated with a t(14;18) frequency > 1 x 10-4 (odds ratio [OR] = 15.52, P < .001) after adjusting for age, sex, time since blood draw, and country of residence. For both the discovery and validation cohorts combined, there was an estimated 23-fold higher risk of subsequent follicular lymphoma in blood samples with a frequency > 1×10-4 (OR =  23.17, P < .001).

Risk by Time Before Diagnosis

For both cohorts, the time between blood draw and diagnosis of incident follicular lymphoma ranged from 2 months to 20 years (average = 7.6 years). Analysis of whether increased t(14;18) frequency was more frequently observed in the prediagnostic samples collected closer to time of diagnosis showed that median time to diagnosis did not differ according to t(14;18) positivity (P = .538) and that there was no significant correlation between t(14;18) level and time to diagnosis among t(14;18)-positive  cases.

A stratified analysis of 5-year intervals (adjusted for matching variables) showed that odds ratios for follicular lymphoma in patients with samples with a frequency > 1×10-4 were 17.17 (P < .001) for samples measured < 5 years before diagnosis, 22.86 (P < .001) for 5 to 10 years, 8.40 (P < .01) for 10 to 15 years, and 5.85 (P = .187) for > 15 years.

The investigators concluded, “High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for [follicular lymphoma], effective years before diagnosis.”

Sandrine Roulland, PharmD, PhD, of Aix-Marseille University, is the corresponding author for the Journal of Clinical Oncology article.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.