Genetic Polymorphism in UDP-Glucuronosyltransferase 2B7 and Colorectal Cancer Risk

Logt, Elise M.J. van der; Morsche, R.H.M. te; Groenendaal, N.; Roelofs, H.M.J.; Metz, M. de; Stappen, J.W. van der; Nagengast, F. M.; Peters, Wilbert H.M.

doi:10.3727/096504009787721203

Cited by 15 publications

(5 citation statements)

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“…A dual-colour allele-specific assay was used for genotyping the polymorphisms at codon 458 of the UGT2B4 gene (rs13119049) and codon 268 of the UGT2B7 gene (rs7439366) PCR was performed on the iCycler iQ Multicolour Real-Time Detection System (Bio-Rad Laboratories) as describe before (24,25). Genotypes were assigned using the iCycler iQ Optical System Software version 3.1.…”

Section: Ugt2b4/ugt2b7mentioning

confidence: 99%

High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk

et al. 2012

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Abstract. Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of carcinogens, may alter enzyme activity and subsequently may play a role in EC etiology. Rather than solely establishing differences in genotype distribution, we investigated whether functional polymorphisms in UGT genes that can predict enzyme activity in vivo, may influence EC risk. A case-control study including 351 Caucasian EC patients and 592 Caucasian controls was conducted and polymorphisms in seven UGT genes were determined, using the polymerase chain reaction. On the basis of allelic in vitro enzyme activity measurements, genotypes were categorized according to their predicted in vivo enzyme activity into high, medium and low categories. Predicted enzyme activity groups were combined and compared between patients and controls. The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly more (OR=1.62; 95% CI, 1.02-2.56) and less frequent (OR=0.36; 95% CI, 0.15-0.84) among patients with esophageal squamous cell carcinoma (ESCC), respectively. High (OR=0.42; 95% CI, 0.22-0.84) and medium (OR=0.25; 95% CI, 0.12-0.52) activity UGT2B4 genotypes were significantly less often present in ESCC patients. No association was detected between UGT genotypes and esophageal adenocarcinoma (EAC) risk. Polymorphisms in UGT genes, resulting in altered enzyme activity genotypes, do not seem modifiers of EAC risk. However, the predicted high activity UGT1A1 genotype, associated with low serum levels of the antioxidant bilirubin, was associated with an increased ESCC risk. The UGT1A8 and UGT2B4 genotypes associated with decreased predicted enzyme activities, were significantly associated with an increased risk of ESCC, probably by a decreased detoxification of carcinogens.

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Section: Ugt2b4/ugt2b7mentioning

confidence: 99%

High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk

et al. 2012

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“…Future research should also put more focus on the association between substrate metabolism and the UGT2B7 c.-161C>T polymorphism and its genotype distribution in different conditions associated with this variant (e.g. oxidative stress, hypertension, atherosclerosis, renal disease, cancer) ( 20 , 21 , 35 , 38 , 39 , 40 , 41 ). As the activity of UGT2B7 encoded by the c .- 161C>T variant allele carriers is substrate-specific and confirmed for different drugs, further research should also focus on examining the clinical relevance of this polymorphism for other substrate drugs such as fenofibrates.…”

Section: Resultsmentioning

confidence: 99%

UGT2B7 c.-161C>T polymorphism frequency in Croatian population

Božina

Ganoci

et al. 2022

Archives of Industrial Hygiene and Toxicology

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Uridine diphosphate glucuronosyltransferase-2B7 (UGT2B7), enzyme responsible for the elimination of a number of xenobiotics through glucuronidation, is expressed in the gut, kidneys, intestines, and brain. However, data on the frequency of UGT2B7 polymorphisms in the Croatian population are limited. The aim of this study was to assess the frequency of the UGT2B7 c.-161C>T (rs7668258) polymorphism in the Croatian population and to compare it with reported frequencies in other populations. This polymorphism is in complete linkage disequilibrium with the UGT2B7 c.802C>T (UGT2B7*2, rs7439366) variant, which is important in clinical medicine. The study reports data of 501 participants from University Hospital Centre Zagreb. All data were collected and analysed retrospectively. Genotyping was performed by real-time polymerase chain reaction (PCR) using the TaqMan® Drug Metabolism Genotyping Assay for UGT2B7 c.-161C>T (rs7668258). We found that 120 (23.95 %) participants were carriers of the UGT2B7 c.-161CC genotype and 255 (50.9 %) were heterozygous carriers (UGT2B7 c.-161CT), while 126 (25.15 %) were homozygous carriers of the variant allele (UGT2B7 c.-161TT). The frequency of the variant UGT2B7 c.-161C>T allele in this study was T=0.506. The frequency of the UGT2B7 c.-161C>T allelic variants and genotypes in the Croatian population is similar to other European populations.

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“…Polymorphism of rs7439366 is a common missense located in exon 2 of UGT 2 B 7 , which may rise the enzymes with either histidine (H) or tyrosine (Y) at amino acid 268. 26 Rs7439366 with a T to C transversion at nucleotide 802, according to Tyr to His conversion at residue 268. The C alleles were 0.489 and 0.732 in Caucasians and Japanese, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…We found rs7439366 was not associated with never‐smoking female NSCLC risk in our study. Polymorphism of rs7439366 is a common missense located in exon 2 of UGT 2 B 7 , which may rise the enzymes with either histidine (H) or tyrosine (Y) at amino acid 268 26 . Rs7439366 with a T to C transversion at nucleotide 802, according to Tyr to His conversion at residue 268.…”

Section: Discussionmentioning

confidence: 99%

Association between sex hormones regulation‐related SNP rs12233719 and lung cancer risk among never‐smoking Chinese women

Qian

Xie

et al. 2021

Cancer Medicine

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Genetic Polymorphism in UDP-Glucuronosyltransferase 2B7 and Colorectal Cancer Risk

Cited by 15 publications

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High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk

High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk

UGT2B7 c.-161C>T polymorphism frequency in Croatian population

Association between sex hormones regulation‐related SNP rs12233719 and lung cancer risk among never‐smoking Chinese women

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