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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1006796728
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin10067967282021-08-03T06:08:19Z EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY CARREON-VALENCIA, TANIA The slow NAT2 N-acetylation genotype inhibits detoxification of a range of monoarylamines and has been associated with increased risk for bladder cancer in cigarette smokers and workers in arylamine dye production. The diarylamine, benzidine, is also a strong bladder carcinogen; however, NAT2 N-acetylation is not key to its detoxification. The purpose of this study was to expand on previous studies that evaluated the impact of NAT2 and GSTM1 polymorphisms on bladder cancer in male subjects exposed only to benzidine. This study also explored possible associations between mutant forms of metabolic enzymes (NAT1, GSTT1, GSTP1, and UGT1A1) and bladder cancer risk. This study included 30 cases and 67 controls exposed occupationally to benzidine in China. In addition, pooled analyses were conducted for NAT2 and GSTM1, incorporating a previous case-control study from the same cohort, for a final study size of 68 cases and 107 controls. NAT2 enzymatic activity was characterized by measuring urinary caffeine metabolite ratios as phenotypic markers. PCR-based methods were used to identify genotypes for the following genes: NAT2, NAT1, GSTM1, GSTT1, GSTP1, and UGT1A1. Using the pooled data adjusted for cumulative benzidine exposure and smoking, a protective association was observed for the slow NAT2 genotype (bladder cancer OR=0.3, 95% CI 0.11-0.99). NAT2 phenotype results were consistent with NAT2 genotype data. The risk of bladder cancer for the GSTM1-null genotype was 1.1 (95% CI 0.58-2.26). Individuals carrying the rapid NAT1 allele showed a higher but not statistically significant risk of bladder cancer (OR=2.3, 95% CI 0.8-7.1). The GSTT1 null polymorphism showed no association with bladder cancer risk; frequencies of the rare alleles for CYP1A1, GSTP1 and UGT1A1 were too low for analysis. Study findings are consistent with other studies conducted in populations exposed only to benzidine. The data actually suggest decreased risk for benzidine-induced bladder cancer among NAT2 slow acetylators, although the mechanism for risk is not clearly understood. These results indicate the existence of key differences in the metabolism of mono- and diarylamines that combine with genotype to affect the individual susceptibility to bladder cancer. 2001-12-03 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1006796728 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1006796728 restricted--full text not available online This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
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NDLTD
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English
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NDLTD
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CARREON-VALENCIA, TANIA
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CARREON-VALENCIA, TANIA
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| author_facet |
CARREON-VALENCIA, TANIA
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CARREON-VALENCIA, TANIA
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| title |
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| title_short |
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| title_full |
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| title_fullStr |
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| title_full_unstemmed |
EFFECT OF GENETIC POLYMORPHISMS OF METABOLIC ENZYMES ON BENZIDINE-INDUCED BLADDER CANCER IN CHINESE WORKERS: A NESTED CASE-CONTROL STUDY
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| title_sort |
effect of genetic polymorphisms of metabolic enzymes on benzidine-induced bladder cancer in chinese workers: a nested case-control study
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University of Cincinnati / OhioLINK
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2001
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http://rave.ohiolink.edu/etdc/view?acc_num=ucin1006796728
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AT carreonvalenciatania effectofgeneticpolymorphismsofmetabolicenzymesonbenzidineinducedbladdercancerinchineseworkersanestedcasecontrolstudy
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1719431545432834048
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