TY - JOUR
T1 - Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes
AU - Hill, Deirdre A.
AU - Wang, Sophia S.
AU - Cerhan, James R.
AU - Davis, Scott
AU - Cozen, Wendy
AU - Severson, Richard K.
AU - Hartge, Patricia
AU - Wacholder, Sholom
AU - Yeager, Meredith
AU - Chanock, Stephen J.
AU - Rothman, Nathaniel
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33751193888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751193888&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-01-026690
DO - 10.1182/blood-2005-01-026690
M3 - Article
C2 - 16857995
AN - SCOPUS:33751193888
SN - 0006-4971
VL - 108
SP - 3161
EP - 3167
JO - Blood
JF - Blood
IS - 9
ER -