Abstract:
OBJECTIVE:Substantial evidence indicates that nonsteroidal anti-inflammatory drugs protect against colorectal cancer by altering cell cycle progression and/or inducing apoptosis, whereas p53 protein is crucial to maintaining cell-cycle arrest and regulating DNA repair, differentiation, and apoptosis. Genetic variants in TP53 gene might therefore influence colorectal cancer risk and modify the effects of nonsteroidal anti-inflammatory drugs. We assessed the association of TP53 Arg72Pro and p53PIN3 polymorphisms with colorectal cancer risk and their possible interaction with nonsteroidal anti-inflammatory drug use. METHODS:We included 467 cases and 563 controls from a population-based case-control study. Multivariate logistic regression analysis was used to estimate the association between genotypes, environmental exposures and colorectal cancer risk, adjusting for potential confounders. RESULTS:Odds ratios of colorectal cancer were 0.75 (95% confidence interval, 0.57-0.99) for TP53 72Pro carriers compared with those homozygous for the TP53 72Arg allele and 0.78 (95% confidence interval, 0.58-1.05) for p53PIN3 A2 carriers compared with p53PIN3 A1A1. Risks differed by nonsteroidal anti-inflammatory drug use. For both investigated TP53 polymorphisms, we found that the colorectal cancer risk associated with regular nonsteroidal anti-inflammatory drug use was statistically significantly modified by the TP53 genotype (P values for interaction=0.049 and 0.034, respectively), whereby a substantial protective effect of nonsteroidal anti-inflammatory drug use was observed for homozygous carriers of the 72Arg allele and of the PIN3 A1 allele (odds ratio 0.44; 95% confidence interval, 0.30-0.65 and odds ratio, 0.45; 95% confidence interval, 0.31-0.65). The interaction between nonsteroidal anti-inflammatory drugs and TP53 genetic polymorphisms was confirmed by haplotype analysis. CONCLUSIONS:These data suggest that the TP53 genotype may modify the influence of nonsteroidal anti-inflammatory drug use on the risk of colorectal cancer. A direct proof of functional analysis is warranted to confirm these findings.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Tan XL,Nieters A,Hoffmeister M,Beckmann L,Brenner H,Chang-Claude Jdoi
10.1097/FPC.0b013e3280d5121csubject
Has Abstractpub_date
2007-08-01 00:00:00pages
639-45issue
8eissn
1744-6872issn
1744-6880pii
01213011-200708000-00008journal_volume
17pub_type
杂志文章abstract::The genetically polymorphic cytochrome P450 2C9 (CYP2C9) metabolizes many important drugs. Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Phenytoin pharmacokinetic i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000174787.92861.91
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens-Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human le...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000153
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000307
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000212
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:Niacin has been used for seven decades to modulate plasma lipids, but its mechanism of action is still unclear. We sought to determine whether variants in the niacin receptor gene, hydroxyl-carboxylic receptor 2 (HCAR2), are associated with lipid response to treatment. PARTICIPANTS AND METHODS:Coding variant...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000289
更新日期:2017-08-01 00:00:00
abstract::Genome-wide studies have identified single nucleotide polymorphisms associated with smoking behaviour and nicotine dependence. Less is known about genetic determinants of smoking cessation, but rs4680 in COMT has recently been shown to explain a substantial proportion of the variation in cessation in the general popul...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32832fabf3
更新日期:2009-08-01 00:00:00
abstract::Asthma is the leading chronic disease in children. Several studies have identified genetic biomarkers associated with susceptibility and severity in both adult and pediatric cases. In this study, we evaluated outcomes in 400 African American and European American pediatric cases all of whom were regular users of inhal...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000355
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVE:As no single nucleotide polymorphism has emerged as pivotal to predict the lack of efficacy and dose-limiting toxicities to methotrexate (MTX), we evaluated the contribution of gene-gene interactions to the effects of this prodrug in rheumatoid arthritis. METHODS:A total of 255 patients treated with MTX for ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833315d1
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVES:To determine whether functional polymorphisms of glutathione S-transferase μ type 1 (GSTM1) and aldehyde dehydrogenase-2 (ALDH2) affect the isosorbide 5-mononitrate (IS-5-MN) response, and the role of the calcitonin gene-related peptide (CGRP) in IS-5-MN response in healthy volunteers. METHODS:A two-phase, ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328343ea0a
更新日期:2011-03-01 00:00:00
abstract::Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has be...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283492af7
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVES:It has been shown that acetaldehyde is an active metabolite of ethanol with central actions that modulate behavior. Catalase has been proposed as the main enzyme responsible for the synthesis of acetaldehyde from ethanol in the brain. Recent studies, however, suggest that cytochrome, in particular the isofor...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328324e726
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset. MATERIALS AND METHODS:One hundred and fifty-two pharmacogenes were selected from liver hepatocellular car...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000097
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Identification of biomarkers that could predict gemcitabine efficacy and toxicity is a key issue in the development of individualized therapy. The aim of our study was to evaluate the influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma (MM). METHODS:In ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834e3572
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single n...
journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
doi:10.1097/01.fpc.0000230412.89973.c0
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND/OBJECTIVES:The polymorphic hepatic enzyme CYP2C19 catalyzes the metabolism of clinically important drugs such as clopidogrel, proton-pump inhibitors, and others and clinical pharmacogenetic testing for clopidogrel is increasingly common. The CYP2C19*10 single-nucleotide polymorphism (SNP) is located 1 bp ups...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000068
更新日期:2014-08-01 00:00:00
abstract::Small heterodimer partner 1 (SHP1, NR0B2) is a member of the superfamily of nuclear receptors (NRs). Even if this orphan receptor, unlike other NRs, lacks the DNA-binding domain, it is capable of regulating transcription by repressing the activity of other NRs by direct protein-protein interaction. Accordingly, SHP1 i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000310
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND/AIM:Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 (CYP) enzymes. The aim of this study was to investigate whether single-nucleotide polymorphisms in the POR gene were correlated with interindividual variations in CYP2B6 activity, as measured by bupropi...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000190
更新日期:2016-02-01 00:00:00
abstract::Rapid development in the annotation of human genetic variation has increased the numbers of single nucleotide polymorphisms (SNPs) in candidate genes by several orders of magnitude. The selection of both useful target SNPs for disease-gene association studies and SNPs associated with the treatment response is therefor...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000194422.12770.fb
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:The effects of various polymorphisms in cytochrome P450 (CYP) enzyme and transporter genes on the pharmacokinetics (PK) of simvastatin were evaluated in healthy Korean men. METHODS:Plasma concentration data for simvastatin and simvastatin acid were pooled from four phase I studies comprising 133 participants...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000176
更新日期:2015-12-01 00:00:00
abstract::Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000286
更新日期:2017-07-01 00:00:00
abstract::A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual varia...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000103
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Corticotropin-releasing hormone receptor (CRHR)-2 participates in smooth muscle relaxation response and may influence acute airway bronchodilator response to short-acting beta2-agonist treatment of asthma. We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in ast...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FPC.0b013e3282fa760a
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000020
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:Human novel oxidoreductase 1 (NDOR1) is a diflavin reductase closely related to cytochrome P450 reductase (POR) and nitric oxide synthase (NOS), which are involved in the metabolism of antitumour agents. A variant cDNA sequence of NDOR1, NDOR1 p.518-519ins9 or NDOR1_v1, has been deposited in GenBank (accessi...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200506000-00002
更新日期:2005-06-01 00:00:00
abstract::Heterotrimeric guanine-binding proteins (G proteins) transmit signals from the cell surface to intracellular signal cascades. The β3-subunit encoded by the gene GNB3 is widely expressed and, therefore, involved in various physiological and pathophysiological processes. A C825T polymorphism located in exon 10 of GNB3 w...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,评审
doi:10.1097/FPC.0b013e3283491153
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. OBJECTIVES:The stud...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32835693f7
更新日期:2012-10-01 00:00:00
abstract::Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200503000-00004
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:Previous studies have shown that polymorphisms in the β2-adrenergic receptor gene (ADRB2) may influence bronchodilator response (BDR) to both β2-agonists and anticholinergics, possibly by intracellular cross-talk, but in opposite ways, in the Japanese population. We hypothesized that the preferential respons...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328349daa1
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVE:The prototypical atypical antipsychotic agent, clozapine, is more efficacious for refractory schizophrenia than the 'typical' antipsychotics, but the mechanism underlying this enhanced efficacy is still under investigation. Since 2002, at least 22 association studies have shown that the DTNBP1 can be associat...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e32832b9cfc
更新日期:2009-06-01 00:00:00
abstract:OBJECTIVE:Paraoxonase-1 (PON1) is synthesized in the liver and is bound to high-density lipoprotein particles in blood. PON1 protects against the development of atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern USA (excluding Florida) has the country's highest age-adjusted mortality rate ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834cebc6
更新日期:2011-12-01 00:00:00