RGD Reference Report - Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer. - Rat Genome Database

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Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer.

Authors: Yuan, JM  Chan, KK  Coetzee, GA  Castelao, JE  Watson, MA  Bell, DA  Wang, R  Yu, MC 
Citation: Yuan JM, etal., Carcinogenesis. 2008 Jul;29(7):1386-93. Epub 2008 Jun 9.
RGD ID: 6906879
Pubmed: PMID:18544563   (View Abstract at PubMed)
PMCID: PMC2720058   (View Article at PubMed Central)
DOI: DOI:10.1093/carcin/bgn136   (Journal Full-text)

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual's susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case-control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19-48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19-1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12-1.81) and 1.71 (1.25-2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12-3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
urinary bladder cancer susceptibilityIAGP 6906879; 6906879DNA:deletion: : (human)RGD 
urinary bladder cancer  IAGP 6906879 RGD 
urinary bladder cancer susceptibilityISOGSTM1 (Homo sapiens)6906879; 6906879DNA:deletion: : (human)RGD 
urinary bladder cancer  ISOGSTP1 (Homo sapiens)6906879; 6906879 RGD 
urinary bladder cancer susceptibilityISOGSTT1 (Homo sapiens)6906879; 6906879DNA:deletion: : (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gstm1  (glutathione S-transferase mu 1)
Gstp1  (glutathione S-transferase pi 1)
Gstt1  (glutathione S-transferase theta 1)

Genes (Mus musculus)
Gstm1  (glutathione S-transferase, mu 1)
Gstp1  (glutathione S-transferase, pi 1)
Gstt1  (glutathione S-transferase, theta 1)

Genes (Homo sapiens)
GSTM1  (glutathione S-transferase mu 1)
GSTP1  (glutathione S-transferase pi 1)
GSTT1  (glutathione S-transferase theta 1)


Additional Information