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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age.

OBJECTIVES: It has been demonstrated that the UDP-glucuronosyltransferase ( UGT) 1A7*3 allele is a risk factor for hepatocellular carcinoma ( HCC) in German and Japanese populations. In this study, therefore, we evaluated the association between UGT1A7 genetic polymorphisms and HCC risk in southern Taiwan, where hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are endemic. METHODS: The 217 HCC patients and 291 controls enrolled in this case-control study were genotyped for UGT1A7 polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Univariate logistic regression analysis revealed that presence of UGT1A7*2 and *3 alleles was associated with HCC risk [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.04 approximately 2.16 and OR = 1.73, 95% CI: 1.19 approximately 2.52, respectively]. Multiple logistic regression analysis demonstrated that significant independent risk factors for HCC were male gender (OR = 2.53, 95% CI: 1.42 approximately 4.52), HBV infection (OR = 13.73, 95% CI: 8.04 approximately 23.46), HCV infection (OR = 83.93, 95% CI: 37.01 approximately 190.32), and low-activity UGT1A7 genotype [high/low (H/L) genotype: OR = 1.93, 95% CI: 1.12 approximately 3.32; low/low (L/L) genotype: OR = 3.06, 95% CI: 1.50 approximately 6.24]. For male HCC patients, significantly earlier onset age was observed for those bearing the UGT1A7 low-activity genotype as opposed to those with the high-activity analogue (median age: 50 vs 59 yr; p < 0.05). CONCLUSIONS: An inverse dose-response relationship was demonstrated between the detoxifying activity of the UGT1A7 genotypes and HCC. Of the male HCC patients, median onset age for those carrying an UGT1A7 low-activity genotype was 9 yr lower than those bearing the high-activity variant.[1]

References

  1. UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age. Tseng, C.S., Tang, K.S., Lo, H.W., Ker, C.G., Teng, H.C., Huang, C.S. Am. J. Gastroenterol. (2005) [Pubmed]
 
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