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Abstract

Title: Risk of Non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes.
Author: Hill DA, Wang SS, Cerhan JR, Davis S, Cozen W, Severson RK, Hartge P, Wacholder S, Yeager M, Chanock SJ, Rothman N
Journal: Blood 108(9):3161-3167
Year: 2006
Month: November

Abstract: Chromosomal translocations, insertions, and deletions are common early events in 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 five 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 1998-2000. Cases were more likely than controls to have the RAG1 820 Arg/Arg (Odds ratio (OR) 2.7; 95% confidence interval (CI) 1.4-5.0) than Lys/Lys genotypes, with evidence of a gene dosage effect (p-trend=0.0008) and less likely to have the LIG4 (DNA Ligase IV) 9 Ile/Ile (OR 0.5; 95% CI 0.3-0.9) than Thr/Thr genotype (p-trend =0.03) in the non-homologous 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.