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<p>Genome-wide association studies (GWAS) have identified germline genetic variants for follicular lymphoma (FL) susceptibility. We conducted a GWAS of prognosis in FL patients to identify genetic predictors of event-free survival (EFS) as well as failure within the first 24 months after treatment initiation (EFS24) using patients treated with rituximab-based immunochemotherapy from three clinical trials and one prospective observational study (<i>N</i> = 1054). Statistical approaches consisted of a pooled GWAS of the four cohorts and a leave-one-cohort-out (LOCO) strategy to identify robust findings that replicated across the four cohorts. The top SNPs for EFS and EFS24 were marked by rs72625024 at 3q27.3 near <i>FETUB</i> and <i>HRG</i> (<i>P</i> = 9.37 × 10<sup>−8</sup>) and rs114695031 at 14q32.13 near <i>TCL6</i> (<i>P</i> = 1.93 × 10<sup>−8</sup>), respectively. These two loci, which were discovered and validated in all 4 LOCO rounds, map near long-non-coding RNAs with putative tumor suppressor functions. Our results pinpoint potential novel biology and the contribution of host genetics to prognosis in FL.</p>

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Genome-wide association study of event-free survival in follicular lymphoma patients treated with front-line immunochemotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月9日

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  • Hervé Ghesquières,
  • Youenn Drouet,
  • Susan L. Slager,
  • Franck Morschhauser,
  • Edith Julia,
  • Sara Galimberti,
  • Dennis Robinson,
  • Melissa C. Larson,
  • Quentin Testard,
  • Bruno Tesson,
  • Jean-François Deleuze,
  • Anne Boland,
  • Emilie Thomas,
  • Christine Lasset,
  • Anne J. Novak,
  • Luc Xerri,
  • Stefano Luminari,
  • Aurelie Verney,
  • Camille Laurent,
  • Lisa M. Rimsza,
  • Thomas M. Habermann,
  • Massimo Federico,
  • Brian K. Link,
  • Gilles Salles,
  • James R. Cerhan

摘要

Genome-wide association studies (GWAS) have identified germline genetic variants for follicular lymphoma (FL) susceptibility. We conducted a GWAS of prognosis in FL patients to identify genetic predictors of event-free survival (EFS) as well as failure within the first 24 months after treatment initiation (EFS24) using patients treated with rituximab-based immunochemotherapy from three clinical trials and one prospective observational study (N = 1054). Statistical approaches consisted of a pooled GWAS of the four cohorts and a leave-one-cohort-out (LOCO) strategy to identify robust findings that replicated across the four cohorts. The top SNPs for EFS and EFS24 were marked by rs72625024 at 3q27.3 near FETUB and HRG (P = 9.37 × 10−8) and rs114695031 at 14q32.13 near TCL6 (P = 1.93 × 10−8), respectively. These two loci, which were discovered and validated in all 4 LOCO rounds, map near long-non-coding RNAs with putative tumor suppressor functions. Our results pinpoint potential novel biology and the contribution of host genetics to prognosis in FL.