title: Metabolic gene variants and risk of non-Hodgkin's lymphoma.
abstract: Genes involved in metabolism of environmental chemical exposures exhibit sequence variability that may mediate the risk of non-Hodgkin's lymphoma. We evaluated associations between non-Hodgkin's lymphoma and 15 variants in AHR, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2E1, GSTP1, GSTM3, EPHX1, NQO1, and PON1. Cases were identified from four Surveillance, Epidemiology, and End Results registries in the United States, and population-based controls were identified through random-digit dialing and Medicare eligibility files. Metabolic gene variants were characterized for the 1,172 (89% of total) cases and 982 (93%) controls who provided biological samples for genotyping. Subjects who were heterozygous or homozygous for the cytochrome P450 gene variant CYP1B1 V432L G allele were at slightly greater risk of non-Hodgkin's lymphoma [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 0.97-1.65]; these results were consistent across B-cell lymphoma subtypes and among both non-Hispanic White and Black subjects, although not statistically significant. The CYP2E1 -1054T allele was associated with decreased risk of non-Hodgkin's lymphoma (CT and TT genotypes combined OR, 0.59; 95% CI, 0.37-0.93), and this pattern was observed among all histologic subtypes. The numbers of cases of particular subtypes were rather small for stable estimates, but we noted that the PON1 L55M AA allele, associated with slightly increased risk of non-Hodgkin's lymphoma (variant homozygotes OR, 1.36; 95% CI, 0.96-1.95), was most strongly associated with follicular non-Hodgkin's lymphoma and T-cell lymphoma, with ORs for variant homozygotes of 2.12 and 2.93, respectively. There was no overall association with non-Hodgkin's lymphoma for the other gene variants we examined. The modest effects we observed may reflect the context of exposures within the general population represented in our study.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, 1100 Fairview Avenue North, M4-B874, Seattle, WA 98109-1024, USA. deroos@u.washington.edu
authors.forename: Anneclaire J
authors.initials: AJ
authors.lastname: De Roos
authors.forename: Laura S
authors.initials: LS
authors.lastname: Gold
authors.forename: Sophia
authors.initials: S
authors.lastname: Wang
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D043303:Aryldialkylphosphatase / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio
chemical_list: D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human