Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes

Blood. 2006 Nov 1;108(9):3161-7. doi: 10.1182/blood-2005-01-026690. Epub 2006 Jul 20.

Abstract

Chromosomal translocations, insertions, and deletions are common early events in non-Hodgkin lymphoma (NHL) carcinogenesis, and implicated in their formation are endogenous processes involved in antigen-receptor diversification, such as V(D)J recombination. DNA repair genes respond to the double- and single-strand breaks induced by these processes and may influence NHL etiology. We examined 34 genetic variants in 19 genes within or related to 5 DNA repair pathways among 1172 cases and 982 matched controls who participated in a population-based NHL study in Los Angeles, Seattle, Detroit, and Iowa from 1998 to 2000. Cases were more likely than controls to have the RAG1 820 R/R (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.4 to 5.0) than Lys/Lys genotypes, with evidence of a gene dosage effect (P trend < .001), and less likely to have the LIG4 (DNA ligase IV) 9 Ile/Ile (OR = 0.5; 95% CI = 0.3 to 0.9) than T/T genotype (P trend = .03) in the nonhomologous end joining (NHEJ)/V(D)J pathway. These NHEJ/V(D)J-related gene variants represent promising candidates for further studies of NHL etiology and require replication in other studies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Repair / genetics*
  • Genetic Variation*
  • Genotype
  • Germ-Line Mutation*
  • Humans
  • Lymphoma, Non-Hodgkin / genetics*
  • Recombination, Genetic
  • Reference Values