Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma.
BACKGROUND
We examined risk of multiple myeloma (MM) associated with variants in genes involved in metabolism and response to exogenous chemicals [cytochrome P450 enzymes (CYP1B1, CYP2C9), epoxide hydrolase (EPHX1), paraoxonase 1 (PON1), arylhydrocarbon hydroxylase receptor (AHR), and NAD(P)H:quinone oxidoreductase (NQO1)].


METHODS
This study included 279 MM cases and 782 controls in a pooled analysis of two population-based case-control studies. One common variant from each candidate gene was genotyped using DNA from blood or buccal cells. We estimated risk of MM associated with each genotype, controlling for race, gender, study site, and age, using odds ratios (OR) and 95% confidence intervals (CI).


RESULTS
Evaluations of the CYP1B1 V432L variant (rs1056836) suggested increased risk of MM among persons with the CG and GG genotypes compared to the CC genotype [OR (95% CI)=1.4 (1.0-2.0)]. Similar results were seen in analyses stratified by race and gender. We did not find any associations between MM and the CYP2C9, EPHX1, NQO1, or PON1 genes.


CONCLUSIONS
CYP1B1 activates chemicals such as polycyclic aromatic hydrocarbons and dioxins to create oxidized, reactive intermediates, and higher gene activity has been shown for the G allele. We conducted the largest analysis to date on MM and these genetic variants and our results provide preliminary evidence that variation in CYP1B1 may influence susceptibility to MM.
Gold
Laura S
LS
Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. lgold@fhcrc.org
De Roos
Anneclaire J
AJ
Brown
Elizabeth E
EE
Lan
Qing
Q
Milliken
Kevin
K
Davis
Scott
S
Chanock
Stephen J
SJ
Zhang
Yawei
Y
Severson
Richard
R
Zahm
Sheila H
SH
Zheng
Tongzhang
T
Rothman
Nat
N
Baris
Dalsu
D
D000328:Adult; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004147:Dioxins / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics*; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism; D012307:Risk Factors
D004147:Dioxins; D011084:Polycyclic Aromatic Hydrocarbons; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1