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Familial predisposition and genetic risk factors for lymphoma

James R. Cerhan and Susan L. Slager

Abstract

Our understanding of familial predisposition to lymphoma (collectively defined as non-Hodgkin lymphoma [NHL], Hodgkin lymphoma [HL], and chronic lymphocytic leukemia [CLL]) outside of rare hereditary syndromes has progressed rapidly during the last decade. First-degree relatives of NHL, HL and CLL patients have an approximately 1.7-fold, 3.1-fold, and 8.5-fold elevated risk of developing NHL, HL and CLL, respectively. These familial risks are elevated for multiple lymphoma subtypes and do not appear to be confounded by non-genetic risk factors, suggesting at least some shared genetic etiology across the lymphoma subtypes. However, a family history of a specific subtype is most strongly associated with risk for that subtype, supporting subtype-specific genetic factors. While candidate gene studies have had limited success in identifying susceptibility loci, genome-wide association studies (GWAS) have successfully identified 67 single nucleotide polymorphisms from 41 loci, predominately associated with specific subtypes. In general, these GWAS-discovered loci are common (minor allele frequency >5%), have small effect sizes (odds ratios of 0.60-2.0), and are of largely unknown function. The relatively low incidence of lymphoma, modest familial risk, and the lack of a screening test and associated intervention all argue against active clinical surveillance for lymphoma in affected families at this time.

  • Submitted April 2, 2015.
  • Accepted September 11, 2015.