Two Inherited Genetic Variants Predict Event-Free and Overall Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy

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James R. Cerhan, MD, PhD

Genetic Variants in Di use Large B-Cell Lymphoma

In a genome-wide association study reported in Journal of Clinical Oncology, Hervé Ghesquieres, MD, PhD, of Centre Léon Bérard, Lyon, France, and colleagues identified two inherited genetic variants that were associated with poorer event-free and overall survival in patients with diffuse large B-cell lymphoma treated with ­immunochemotherapy.1

James R. Cerhan, MD, PhD, of Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

Study Details

The study involved meta-analysis of genome-wide association study data sets from the LNH2003B trial (N = 540), a prospective clinical trial from the Lymphoma Study Association, and the Molecular Epidemiology Resource study (N = 312), a prospective observational study from the University of Iowa-Mayo Clinic Lymphoma Specialized Program of Research Excellence. Top single-nucleotide polymorphisms were genotyped in independent cohorts of patients from the Specialized Program of Research Excellence (N = 391) and the Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang-075 randomized trial (N = 294). Hazard ratios (HRs) for event-free and overall survival were calculated using a model adjusting for age, sex, and age-adjusted International Prognostic Index (IPI).

In a meta-analysis of the four studies, the top loci associated with event-free survival were marked by rs7712513 at 5q23.2, near SNX2 and SNCAIP (HR = 1.39, P = 2.08 × 10-7), and rs7765004 at 6q21, near MARCKS and HDAC2 (HR = 1.38, P = 7.09 × 10-7); however, neither reached the conventional threshold for genome-wide significance (P = 5 × 10-8). Both rs7712513 (HR = 1.49, P = 3.53 × 10-8) and rs7765004 (HR = 1.47, P = 5.36 × 10-7) were also associated with overall survival.

In an exploratory analysis, a risk score based on the two single-nucleotide polymorphisms was highly predictive of event-free survival (P = 1.78 × 10-12) independent of treatment, IPI, and cell of origin.

The investigators concluded: “Our study provides encouraging evidence for associations between loci at 5q23.2 and 6q21 with [event-free survival] and [overall survival] in patients with diffuse large B-cell lymphoma treated with immunochemotherapy, suggesting novel biology and the potential contribution of host genetics to the prognosis of this aggressive malignancy.” ■

Disclosure: The study was supported by National Cancer Institute Specialized Programs of Research Excellence (SPORE) in Human Cancer, Molecular Epidemiology of Non-Hodgkin Lymphoma Survival, National Center for Advancing Translational Science, Henry J. Predolin Foundation, Institut National du Cancer, Lymphoma Study Association, Fondation de France, and Philippe Foundation. For full disclosures of the study authors, visit


1. Ghesquieres H1, Slager SL1, Jardin F, et al: Genome-wide association study of event-free survival in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol 33:3930-3937, 2015.