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Abstract: Gene polymorphisms of the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism-related enzymes-cytochrome P450 (CYP) monooxygenase 2A13 (CYP2A13) and UDP-glucuronosyltransferases (UGT)-2B7 could contribute to the levels of NNK-related metabolites in urine, thereby increasing the susceptibility to urothelial carcinoma (UC). Therefore, our study aimed to evaluate the roles of two gene polymorphisms (CYP2A13 and UGT2B7) of NNK metabolism-related enzymes in the carcinogenesis of UC in Taiwan. A hospital-based pilot case–control study was conducted. There were 121 UC cases and 121 age- and sex-matched healthy participants recruited from March 2007 to April 2009. Urine samples were analyzed for NNK-related metabolites using the liquid chromatography–tandem mass spectrometry method. Genotyping was conducted using a polymerase chain reaction-restriction fragment length polymorphism technique. ANCOVA and multivariate logistic regression were applied for data analyses. In healthy controls, former smokers had significantly higher total NNAL and higher NNAL-Gluc than never smokers or current smokers. Subjects carrying the UGT2B7 268 His/Tyr or Tyr/Tyr genotype had significantly lower total NNAL than those carrying His/His genotype. However, no association was seen between gene polymorphisms of CYP2A13 and UGT2B7 and UC risk after adjustment for age and sex. Significant dose -response associations between total NNAL, free NNAL, the ratios of free NNAL/total NNAL and NNAL-Gluc/total NNAL and UC risk were observed. In the future, large-scale studies will be required to verify the association between the single nucleotide polymorphisms of NNK metabolism-related enzymes and UC risk. [Copyright &y& Elsevier]

Introduction: Results of several studies have indicated that the variation of c.-3279T>G in the UDP-glucuronosyltransferase (UGT)1A1 gene could be a further factor for the development of hyperbilirubinemia. However, this variant has not been reported in the Taiwanese population. Materials & methods: PCR-restriction fragment length polymorphism was utilized to determine variants at nucleotides -3279 (*60), -53 (*28) and 211 (*6) in the UGT1A1 gene for 178 Taiwanese hyperbilirubinemic patients and 200 controls. Results: A total of ten and nine diplotypes were observed in the hyperbilirubinemic patients and controls, respectively. Subjects possessing diplotypes of compound haplotypes (*60/*28, *60/*6, *1/*60 plus *1/*28 plus *1/*6); *60/*60; *60/*60 plus 1/*28 and *6/*6 were significantly related to hyperbilirubinemia development, with an odds ratio of 7.83-188.00 (p = 0.012~ <0.001). A subgroup possessing diplotypes of *60/*60 plus *28/*28 were only found in hyperbilirubinemic patients, not in the controls. Bilirubin concentration amongst these patients carrying a diplotype of *60/*60 plus *28/*28 (mean [SD]: 39.2 [10.77] µmol/l) was significantly higher than that in the diplotype subgroups of *60/*60 plus *1/*28 (30.4 [4.10] µmol/l) and *6/*6 (30.3 [3.08] µmol/l) (p = 0.046 and 0.034, respectively). Conclusions: The c.-3279T>G variant is a further factor for the development of hyperbilirubinemia. Our results also demonstrate that possessing the *60/*60 plus *28/*28 diplotype in the UGT1A1 gene is a determinant of relatively higher bilirubin values amongst hyperbilirubinemic patients. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, multiple chemotherapeutic agent-related genetic polymorphisms, including dihydropyrimidine dehydrogenase (DPD) IVS14+1 G>A, UGT1A1 3156 G>A, and UDP-glucuronosyltransferase (UGT)1A1 28 tandem repeats, were analyzed in patients with colorectal cancer and studied in correlation with the clinical features of those patients. The genotypes from 273 patients with stages I–IV colorectal cancer who underwent operations were determined by means of polymerase chain reaction-restriction fragment length polymorphism. The results showed that the genotype distribution of DPD GG, UGT1A1 3156 GG, and UGT1A1 28 tandem repeats 5/6 or 6/6 in Taiwanese subjects were 98.4%, 82.2%, and 80.6%, respectively. After analysis of the relationship between the genotypes and clinicopathological data of the patients, a significant correlation was observed between vascular invasion in patients with genetic polymorphisms ofDPDGG, UGT1A13156GG, and UGT1A1 28 repeat 5/6 or 6/6 (OR: 2.236, p = 0.015). There was a statistical correlation between vascular invasion and tumor invasion, lymph node metastasis, cancer stage, differentiation, perineural invasion, and survival (all p < 0.05). The results of the present study highly suggest that DPDGG, UGT1A13156GG, and UGT1A1 28 repeat 5/6 or 6/6 genotypes and vascular invasion could be prognostic factors for Taiwanese patients with colorectal cancer. [Copyright &y& Elsevier]