Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes.
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.
Hill
Deirdre A
DA
Cancer Center and Department of Internal Medicine, UNM School of Medicine, 1 University of New Mexico, MSC 10 5550, Albuquerque, NM 87131-0001, USA. dahill@salud.unm.edu
Wang
Sophia S
SS
Cerhan
James R
JR
Davis
Scott
S
Cozen
Wendy
W
Severson
Richard K
RK
Hartge
Patricia
P
Wacholder
Sholom
S
Yeager
Meredith
M
Chanock
Stephen J
SJ
Rothman
Nathaniel
N
D004260:DNA Repair / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D011995:Recombination, Genetic; D012016:Reference Values