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

Deirdre A. Hill, Sophia S. Wang, James R. Cerhan, Scott Davis, Wendy Cozen, Richard K. Severson, Patricia Hartge, Sholom Wacholder, Meredith Yeager, Stephen J. Chanock, Nathaniel Rothman

Research output: Contribution to journalArticle

62 Scopus citations

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 populationbased 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.

Original languageEnglish (US)
Pages (from-to)3161-3167
Number of pages7
JournalBlood
Volume108
Issue number9
DOIs
StatePublished - Nov 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Hill, D. A., Wang, S. S., Cerhan, J. R., Davis, S., Cozen, W., Severson, R. K., Hartge, P., Wacholder, S., Yeager, M., Chanock, S. J., & Rothman, N. (2006). Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes. Blood, 108(9), 3161-3167. https://doi.org/10.1182/blood-2005-01-026690