TY - JOUR
T1 - Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes
AU - Figueroa, Jonine D.
AU - Malats, Núria
AU - García-Closas, Montserrat
AU - Real, Francisco X.
AU - Silverman, Debra
AU - Kogevinas, Manolis
AU - Chanock, Stephen
AU - Welch, Robert
AU - Dosemeci, Mustafa
AU - Lan, Qing
AU - Tardón, Adonina
AU - Serra, Consol
AU - Carrato, Alfredo
AU - García-Closas, Reina
AU - Castaño-Vinyals, Gemma
AU - Rothman, Nathaniel
N1 - Funding Information:
We thank Robert C.Saal from Westat, Rockville, MD, and Leslie Carroll and Jane Wang from Information Management Services, Silver Spring, MD, for their support in study and data management; Doug Richesson from Division of Cancer Epidemiology and Genetics, National Cancer Institute, for his support in data analysis, Dr Maria Sala from Institut Municipal d’Investigació Mèdica, Barcelona, Spain, for her work in data collection; Francisco Fernandez for his work on data management, Dr Montserrat Torà for her work in the coordination of sample collection and blood processing and physicians, nurses, interviewers and study participants for their efforts during field work. We would also like to thank Dr Idan Menashe and Dr Kai Yu for statistical advice in haplotype and CART analyses. Lastly, J.D.F. would like to thank the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, for their support.
PY - 2008
Y1 - 2008
N2 - Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (∼90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.
AB - Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (∼90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.
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U2 - 10.1093/carcin/bgn163
DO - 10.1093/carcin/bgn163
M3 - Article
C2 - 18632753
AN - SCOPUS:53449099969
SN - 0143-3334
VL - 29
SP - 1955
EP - 1962
JO - Carcinogenesis
JF - Carcinogenesis
IS - 10
ER -