TY - JOUR
T1 - Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma
AU - Gold, Laura S.
AU - De Roos, Anneclaire J.
AU - Brown, Elizabeth E.
AU - Lan, Qing
AU - Milliken, Kevin
AU - Davis, Scott
AU - Chanock, Stephen J.
AU - Zhang, Yawei
AU - Severson, Richard
AU - Zahm, Sheila H.
AU - Zheng, Tongzhang
AU - Rothman, Nat
AU - Baris, Dalsu
N1 - Funding Information:
This work was partially supported by training grant T32ES07262 from National Institutes of Health, National Institute of Environmental Health Sciences and by the Intramural Research Program of the National Institutes of Health .
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Arylhydrocarbon hydroxylase receptor (AHR)
KW - Cytochrome P450 enzymes (CYP1B1, CYP2C9)
KW - Epoxide hydrolase (EPHX1)
KW - Multiple myeloma
KW - NAD (P) H: quinone oxidoreductase (NQO1)
KW - Paraoxonase 1 (PON1)
UR - http://www.scopus.com/inward/record.url?scp=70349757186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349757186&partnerID=8YFLogxK
U2 - 10.1016/j.canep.2009.08.005
DO - 10.1016/j.canep.2009.08.005
M3 - Article
C2 - 19736056
AN - SCOPUS:70349757186
SN - 1877-7821
VL - 33
SP - 276
EP - 280
JO - Cancer Epidemiology
JF - Cancer Epidemiology
IS - 3-4
ER -