Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

Parmar, Sumit; Stingl, Julia C.; Huber-Wechselberger, Ariana; Kainz, Alexander; Renner, Wilfried; Langsenlehner, Uwe; Krippl, Peter; Brockmöller, Jürgen; Haschke-Becher, Elisabeth

doi:10.1186/bcr2894

Cited by 38 publications

(28 citation statements)

References 47 publications

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“…The impact of UGT2B7 polymorphisms on the metabolism of drugs used to treat breast cancer has also been investigated. For example, the UGT2B7 rs7668258 C>T polymorphism has been associated with the metabolism, efficacy and toxicity of epirubicin chemotherapy in breast cancer patients . Moreover, UGT2B7 802Tyr has been suggested as a candidate biomarker for a good response to tamoxifen therapy in patients with breast cancer …”

Section: Discussionmentioning

confidence: 99%

Association between UDP‐glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females

Qiao

Lam

Zhao

et al. 2018

Clin Exp Pharma Physio

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Summary This retrospective study was performed to evaluate the association between the UGT2B7 tagSNPs (rs12233719, rs4356975, rs7435335 and rs7441774) and breast cancer in Chinese females. Blood samples were collected from 672 patients with breast cancer and 670 healthy controls for DNA extraction. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used to analyze UGT2B7 polymorphisms. Dual‐luciferase reporter assays were further performed to investigate the regulatory function of UGT2B7 tagSNPs. The frequency of rs7441774 G allele in the breast cancer cases was statistically significantly higher than in the controls (0.412 vs 0.358, P = .006; odds ratio [OR] = 1.27, 95% CI = 1.08‐1.48). After adjusting for conventional risk factors, individuals with the GG genotype had a higher breast cancer risk than those with the AA genotype (adjusted OR = 1.63, 95% CI = 1.18‐2.26; P = .008). The GCGG haplotype of UGT2B7 was also associated with breast cancer (OR = 1.22, 95% CI = 1.04‐1.45; P = .027). Meanwhile, the rs7441774 G allele could significantly decrease the transcriptional activity of the UGT2B7 gene. This study indicates that UGT2B7 polymorphisms may play a crucial role in the occurrence and development of breast cancer in the Han Chinese population.

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Section: Discussionmentioning

confidence: 99%

Association between UDP‐glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females

Qiao

Lam

Zhao

et al. 2018

Clin Exp Pharma Physio

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“…It also conjugates various classes of major drugs including analgesics, carboxylic non-steroidal anti-inflammatory drugs, and anti-carcinogens 9. In addition, UGT2B7 polymorphisms were found to have associations with an increased risk of bladder cancer, colorectal cancer, and a treatment method for breast cancer 10-1213.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Variant Screening of the UGT Gene Family

et al. 2014

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PurposeUGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs.Materials and MethodsWe directly sequenced 288 subjects consisting of 96 Korean, 48 Japanese, 48 Han Chinese, 48 African American, and 48 European American subjects. Subsequently, we analyzed genetic variability, linkage disequilibrium (LD) structures and ethnic differences for each gene. We also conducted in silico analysis to predict the function of novel SNPs.ResultsA total of 87 SNPs were detected, with seven pharmacogenetic core SNPs and 31 novel SNPs. We observed that the frequencies of UGT1A1 *6 (rs4148323), UGT1A1 *60 (rs4124874), UGT1A1 *93 (rs10929302), UGT2B7 *2 (rs7439366), a part of UGT2B7 *3 (rs12233719), and UGT2B15 *2 (rs1902023) were different between Asian and other ethnic groups. Additional in silico analysis results showed that two novel promoter SNPs of UGT1A1 -690G>A and -689A>C were found to potentially change transcription factor binding sites. Moreover, 673G>A (UGT2B7), 2552T>C, and 23269C>T (both SNPs from UGT2B15) changed amino acid properties, which could cause structural deformation.ConclusionFindings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.

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“…UGT2B7 contributes to glucosidation of hydesoxycholic acid in the liver, as well as glucuronidation of steroid hormones and fatty acids, and to the detoxification of cholestatic bile acids and may have a role in the formation of proximal carcinogens, such as quinine estrogens . In patients with BC that carried the rs7439366, they might have had a benefit after adjuvant epirubicin‐based treatment . Nieuweboer et al .…”

Section: Discussionmentioning

confidence: 99%

Polymorphic Variants in NR1I3 and UGT2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case‐Control Study

Arbitrio

Scionti

Altomare

et al. 2019

Clin Pharma and Therapeutics

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Taxane‐related peripheral neuropathy (TrPN) is a dose‐limiting toxicity with important interindividual variability. Genetic polymorphisms in absorption, distribution, metabolism, and excretion (ADME) genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix drug‐metabolizing enzyme and transporter microarray platform, in a retrospective case‐control study, the correlation between ADME polymorphic variants and grades ≥ 2−3‐TrPN was investigated. In a breast cancer (BC) training set, five single‐nucleotide polymorphisms in NR1I3 and UDP‐glucuronosyltransferase (UGT)2B7 genes were correlated to grades ≥ 2−3‐TrPN protection. By receiver operating characteristic curves, the grades ≥ 2−3‐TrPN‐related candidate biomarkers in an independent series of 54 patients with BC (17 cases and 37 controls) were validated. NR1I3 was correlated to paclitaxel‐TrPN and UGT2B7 to docetaxel‐TrPN. Moreover, a genetic signature of prognostic relevance for BC outcome was found. Our findings might have potential relevance for personalized management of patients with BC for prevention of treatment failure in ultrametabolizer genetic variants.

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Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

Cited by 38 publications

References 47 publications

Association between UDP‐glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females

Association between UDP‐glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females

Comprehensive Variant Screening of the UGT Gene Family

Polymorphic Variants in NR1I3 and UGT2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case‐Control Study

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