Effect of genetic polymorphisms on therapeutic response and clinical outcomes in pancreatic cancer patients treated with gemcitabine.

Abstract:

AIM:Gemcitabine is the first chemotherapeutic agent to show clinical benefits in pancreatic cancer patients. While interindividual variability in chemoresponse is observed, genetic factors that affect drug metabolism have not been clearly defined. The purpose of this study is to evaluate the relationships between genetic polymorphisms and therapeutic efficacy in pancreatic cancer patients treated with gemcitabine. PATIENTS & METHODS:The study population consisted of 102 pancreatic cancer patients who had been treated with a gemcitabine-based chemotherapeutic regimen. 102 genetic polymorphisms were selected from 23 genes involved in the metabolism and action sites of gemcitabine and screened for polymorphisms using the MassARRAY(®) system. The polymorphisms and haplotypes were analyzed in relation to overall survival (OS), time-to-progression (TTP) and disease progression. RESULTS:CMPK1 360C>T was significantly associated with OS, TTP and disease progression (p = 0.042, 0.007 and 0.040, respectively, in a dominant genetic model). Additionally, CMPK1 240G>T was correlated with OS and TTP. The frequencies of the haplotypes for the CMPK1, SLC28A1, DCTD and TLE4 genes differed according to disease progression. CONCLUSION:Genetic polymorphisms in genes related to metabolism and action sites of gemcitabine showed associations with the therapeutic efficacy, in terms of OS, TTP and disease progression in pancreatic cancer patients treated with gemcitabine-based chemotherapy. In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Woo HI,Kim KK,Choi H,Kim S,Jang KT,Yi JH,Park YS,Park JO,Lee SY

doi

10.2217/pgs.12.82

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

1023-35

issue

9

eissn

1462-2416

issn

1744-8042

journal_volume

13

pub_type

杂志文章
  • MTRR rs1801394 and its interaction with MTHFR rs1801133 in colorectal cancer: a case-control study and meta-analysis.

    abstract:AIM:This study aims to evaluate the association between the MTRR rs1801394 alone or in interaction with the MTHFR rs1801133 and susceptibility to colorectal cancer (CRC) and its characteristics in Iranian population. Additionally, both a systematic review and meta-analysis were performed to derive a more precise assess...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,meta分析

    doi:10.2217/pgs-2017-0030

    authors: Haerian MS,Haerian BS,Molanaei S,Kosari F,Sabeti S,Bidari-Zerehpoosh F,Abdolali E

    更新日期:2017-07-01 00:00:00

  • HLA-DRB1*1501 and VDR polymorphisms and survival of Mycobacterium tuberculosis in human macrophages exposed to inhalable microparticles.

    abstract:AIM:We examined whether HLA-DRB1*1501 and four VDR SNPs influence the macrophage response to infection with Mycobacterium tuberculosis (Mtb) via innate immune versus drug treatment or drug delivery mechanisms. MATERIALS & METHODS:Monocyte-derived macrophages from 24 healthy donors were infected with Mtb in vitro. Surv...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.13.12

    authors: Singh AK,Abhimanyu,Yadav AB,Sharma S,Garg R,Bose M,Misra A

    更新日期:2013-04-01 00:00:00

  • SimuGen Ltd: reliable, early prediction of drug toxicity with toxicogenomics, human cell culture and computational models.

    abstract::Toxicogenomics is, arguably, the most exciting endeavor to better understand and/or predict the toxicity of drugs during their development, using technologies such as gene-expression microarrays. Through much of its (sometimes overzealous) build-up, toxicogenomics has found a natural niche as a bioinformatics and/or p...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/14622416.8.8.1081

    authors: Wills Q

    更新日期:2007-08-01 00:00:00

  • A potential role for the CDH13/CDH15 gene in repeat revascularization after first percutaneous coronary intervention.

    abstract::Aim: Major drawbacks of percutaneous coronary intervention are the high occurrence of repeat revascularization due to restenosis and disease progression. The aim of this study was to find genetic indicators to predict the risk of repeat revascularization. Materials & methods: From April 2015 to June 2016, 143 patients...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2019-0118

    authors: Xiang Q,Liu Z,Lu Y,Mao J,Chen S,Zhao X,Zhou S,Xie Q,Wang Z,Mu G,Jiang J,Gong Y,Cui Y

    更新日期:2020-01-01 00:00:00

  • Applicability of gene expression and systems biology to develop pharmacogenetic predictors; antipsychotic-induced extrapyramidal symptoms as an example.

    abstract::Pharmacogenetics has been driven by a candidate gene approach. The disadvantage of this approach is that is limited by our current understanding of the mechanisms by which drugs act. Gene expression could help to elucidate the molecular signatures of antipsychotic treatments searching for dysregulated molecular pathwa...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.15.134

    authors: Mas S,Gassó P,Lafuente A

    更新日期:2015-11-01 00:00:00

  • MicroRNAs and pharmacogenomics.

    abstract::Pharmacogenomics studies the influence of genomics on drug response safety and efficacy. Although research in this field was initiated many years ago, few functional applications are currently in use at the clinic. MicroRNAs (miRNAs) are short noncoding RNAs that bind genes and silence their expression. MiRNAs are enc...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.10.26

    authors: Shomron N

    更新日期:2010-05-01 00:00:00

  • Integrating pharmacogenomics into drug development.

    abstract::The first observations of inherited differences in drug effects in the 1950s led to the recognition of a genetic basis for drug response. With the development of genetics and molecular biology, it became clear that certain drug responses could be associated with specific genetic variations or polymorphisms. There are ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.3.4.453

    authors: Ferentz AE

    更新日期:2002-07-01 00:00:00

  • Conference Scene: Systems biology and personalized health science and translation.

    abstract::After a 1-day advanced course on systems biology, the main themes of this 3-day colloquium were developed: from systems biology to systems medicine with special applications to cancer; pharmacogenomics in drug discovery and clinical application; and epigenomics and genome-wide association studies in cardiovascular dis...

    journal_title:Pharmacogenomics

    pub_type:

    doi:10.2217/pgs.13.201

    authors: Siest G,Ndiaye NC,El Shamieh S,Shahabi P,Stathopoulou M,Saleh AS,Godjo T,Albertini L,Visvikis-Siest S

    更新日期:2013-12-01 00:00:00

  • Impact of genotype-guided dosing on anticoagulation visits for adults starting warfarin: a randomized controlled trial.

    abstract:AIM:This study aimed to assess the effectiveness of genotype-guided warfarin dosing. PATIENTS & METHODS:A total of 109 adults were randomized to receive initial dosing as determined by an algorithm containing genetic (VKORC1 and CYP2C9) plus clinical information or only clinical information. Primary end points were th...

    journal_title:Pharmacogenomics

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2217/pgs.13.145

    authors: Jonas DE,Evans JP,McLeod HL,Brode S,Lange LA,Young ML,Shilliday BB,Bardsley MM,Swinton-Jenkins NJ,Weck KE

    更新日期:2013-10-01 00:00:00

  • CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen.

    abstract:AIMS:Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme act...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.10.112

    authors: Ruiter R,Bijl MJ,van Schaik RH,Berns EM,Hofman A,Coebergh JW,van Noord C,Visser LE,Stricker BH

    更新日期:2010-10-01 00:00:00

  • Pharmacogenovigilance: a pharmacogenomics pharmacovigilance program.

    abstract::In this report, we review the importance of pharmacovigilance in detecting postmarketing adverse drug events and the potential for developing pharmacogenovigilance programs by integrating pharmacogenomics with pharmacovigilance. We propose to start developing such a program in primary healthcare systems that use basic...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.14.44

    authors: Awada Z,Zgheib NK

    更新日期:2014-04-01 00:00:00

  • Suppression of miR-628-3p and miR-641 is involved in rifampin-mediated CYP3A4 induction in HepaRG cells.

    abstract:AIM:This study aimed to explore the role of miRNAs in rifampin-mediated induction of CYP3A4 in HepaRG cells. MATERIALS & METHODS:Microarray was performed to determine the expression of miRNAs in rifampin-treated HepaRG cells, followed by bioinformatics and luciferase reporter gene assay to analyze miRNAs that directly...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2016-0088

    authors: Yan L,Liu J,Zhao Y,Nie Y,Ma X,Kan Q,Zhang L

    更新日期:2017-01-01 00:00:00

  • Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study.

    abstract:BACKGROUND:Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. AIM:The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response t...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.119

    authors: Frau F,Zaninello R,Salvi E,Ortu MF,Braga D,Velayutham D,Argiolas G,Fresu G,Troffa C,Bulla E,Bulla P,Pitzoi S,Piras DA,Glorioso V,Chittani M,Bernini G,Bardini M,Fallo F,Malatino L,Stancanelli B,Regolisti G,Ferri

    更新日期:2014-09-01 00:00:00

  • Beta-adrenergic receptor polymorphisms and drug responses in asthma.

    abstract::Genetic variation in the beta 2-adrenoceptor and its associated proteins is common and therefore potentially relevant to the clinician. Several functional SNPs have been described but in vitro studies have yielded inconsistent results. Confounding due to the variable presence of other polymorphic alleles may be the ex...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.1517/14622416.3.2.173

    authors: Taylor DR,Kennedy MA

    更新日期:2002-03-01 00:00:00

  • The current and future state of pharmacogenomics medical education in the USA.

    abstract::Healthcare professionals (e.g., physicians, physician assistants, pharmacists, nurses and genetic counselors) believe pharmacogenomics (PGx) is essential to personalized medicine; however, they still lack confidence prescribing, dosing, interacting with other healthcare professionals and counseling patients with regar...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.12.113

    authors: Nickola TJ,Green JS,Harralson AF,O'Brien TJ

    更新日期:2012-09-01 00:00:00

  • Classical twin design in modern pharmacogenomics studies.

    abstract::Response to medication is highly variable, unpredictable and, at times, may be fatal. All drugs are more effective in certain groups of the population while showing no or minimal benefit in other groups. Although the current data on the subject are piecemeal, anecdotal evidence suggests that, in line with other common...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs.09.171

    authors: Rahmioğlu N,Ahmadi KR

    更新日期:2010-02-01 00:00:00

  • Fibrate pharmacogenomics: expanding past the genome.

    abstract::Fibrates are a medication class prescribed for decades as 'broad-spectrum' lipid-modifying agents used to lower blood triglyceride levels and raise high-density lipoprotein cholesterol levels. Such lipid changes are associated with a decrease in cardiovascular disease, and fibrates are commonly used to reduce risk of ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2019-0140

    authors: House JS,Motsinger-Reif AA

    更新日期:2020-03-01 00:00:00

  • Advancing psychiatric pharmacogenomics using drug development paradigms.

    abstract::Drugs used to treat psychiatric disorders, even when taken as directed, fail to provide adequate relief for a sizeable proportion of patients. Despite our advancements in understanding human genetics and development of high-throughput tools to probe variation, pharmacogenomics has yielded marginal ability to predict d...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs-2017-0104

    authors: Smith RM

    更新日期:2017-10-01 00:00:00

  • Pharmacogenomics and the treatment of acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous malignancy that is primarily treated with combinations of cytarabine and anthracyclines. Although this scheme remains effective in most of the patients, variability of outcomes in patients has been partly related with their genetic variability...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs-2016-0055

    authors: Megías-Vericat JE,Montesinos P,Herrero MJ,Bosó V,Martínez-Cuadrón D,Poveda JL,Sanz MÁ,Aliño SF

    更新日期:2016-07-01 00:00:00

  • Strengths and weaknesses of pharmacogenetic studies of antipsychotic drugs: the potential value of the PEPs study.

    abstract::The successful application of pharmacogenetics in routine clinical practice is still a long way from becoming a reality. In order to favor the transfer of pharmacogenetic results to clinical practice, especially in psychiatry, these studies must be optimized. This article reviews the strengths and weaknesses that char...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,多中心研究,评审

    doi:10.2217/pgs.12.159

    authors: Mas S,Llerena A,Saíz J,Bernardo M,Lafuente A

    更新日期:2012-11-01 00:00:00

  • Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance.

    abstract:OBJECTIVES:Three exonic single nucleotide polymorphisms (SNPs) in the cytochrome P450 2B6 (CYP2B6) gene, 516G>T, 785A>G and 1459C>T, have been described to be associated with functional changes in the CYP2B6 catalytic activity or protein expression. They are therefore of potential clinical importance for drug efficacy ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/14622416.7.7.995

    authors: Rohrbacher M,Kirchhof A,Geisslinger G,Lötsch J

    更新日期:2006-10-01 00:00:00

  • Pharmacokinetic and CYP3A5 pharmacogenetic differences between once- and twice-daily tacrolimus from the first dosing day to 1 year after renal transplantation.

    abstract:UNLABELLED:Aim & patients & methods: This study investigated 24-h pharmacokinetic and CYP3A5 pharmacogenetic differences between once-daily tacrolimus (Tac-q.d.) versus twice-daily tacrolimus (Tac-b.i.d.) pretransplantation and at 1 month and 1 year post-transplantaion. RESULTS:The dose-adjusted trough level (Cmin) an...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.98

    authors: Satoh S,Niioka T,Kagaya H,Numakura K,Inoue T,Saito M,Komine N,Narita S,Tsuchiya N,Habuchi T,Miura M

    更新日期:2014-08-01 00:00:00

  • Gene expression correlates of unexplained fatigue.

    abstract::Quantitative trait analysis (QTA) can be used to test whether the expression of a particular gene significantly correlates with some ordinal variable. To limit the number of false discoveries in the gene list, a multivariate permutation test can also be performed. The purpose of this study is to identify peripheral bl...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/14622416.7.3.395

    authors: Whistler T,Taylor R,Craddock RC,Broderick G,Klimas N,Unger ER

    更新日期:2006-04-01 00:00:00

  • HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican Mestizo patients.

    abstract:AIM:Several HLA alleles have been associated with antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) in different populations; however, this has not been investigated in Mexican Mestizos (MM). Thus, the purpose of this preliminary study was to determine the association of HLA class I alleles wi...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.14.135

    authors: Fricke-Galindo I,Martínez-Juárez IE,Monroy-Jaramillo N,Jung-Cook H,Falfán-Valencia R,Ortega-Vázquez A,Alonso-Vilatela ME,López-López M

    更新日期:2014-01-01 00:00:00

  • Functional characterization of CYP2D7 gene variants.

    abstract::The ultrarapid CYP2D6 metabolizer (UM) phenotype is caused by CYP2D6 gene duplications in some, but not all, UM individuals. CYP2D6 and the adjacent pseudogene CYP2D7 are highly homologous; however, CYP2D7 harbors a premature stop codon, which is absent in carriers of the rare CYP2D7 variant rs530303678. We addressed ...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2018-0065

    authors: Jukic MM,Lauschke VM,Saito T,Hiratsuka M,Ingelman-Sundberg M

    更新日期:2018-08-01 00:00:00

  • The genetics of fibromyalgia syndrome.

    abstract::Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically p...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/14622416.8.1.67

    authors: Buskila D,Sarzi-Puttini P,Ablin JN

    更新日期:2007-01-01 00:00:00

  • A review of consent practices and perspectives for pharmacogenetic testing.

    abstract:AIM:We aimed to understand consent practices for pharmacogenetic (PGx) testing. METHODS:We conducted a literature review and analysis of consent forms from clinical laboratories offering PGx testing. RESULTS:Our review of the literature shows a lack of consensus about the need for and type of informed consent for PGx...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章,评审

    doi:10.2217/pgs-2016-0039

    authors: Haga SB,Mills R

    更新日期:2016-09-01 00:00:00

  • History repeats itself: the family medication history and pharmacogenomics.

    abstract::Related to many drug gene-product interactions, application of pharmacogenomics can lead to improved medication efficacy while decreasing or avoiding adverse drug reactions. However, utilizing pharmacogenomics without other information does not allow for optimal medication therapy. Currently, there is a lack of docume...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs-2015-0015

    authors: Smith TR,Kearney E,Hulick PJ,Kisor DF

    更新日期:2016-05-01 00:00:00

  • Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment.

    abstract:AIMS:The importance of polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD) for the prediction of severe toxicity in 5-fluorouracil (5-FU)-based chemotherapy is still unclear. This study aims to assess the predictive value of DPYD variation with respect to previously described DPYD variants for 5-FU toxicit...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.09.28

    authors: Amstutz U,Farese S,Aebi S,Largiadèr CR

    更新日期:2009-06-01 00:00:00

  • Genetic polymorphisms in GST genes and survival of colorectal cancer patients treated with chemotherapy.

    abstract:UNLABELLED:Glutathione S-transferases (GSTs) participate in the detoxification of chemotherapeutic agents. Genetic polymorphisms in GST genes (GSTP1 Ile105Val, copy-number variants of GSTM1 and GSTT1) that lead to diminished enzyme activity have been associated with increased chemotherapeutic treatment benefit in color...

    journal_title:Pharmacogenomics

    pub_type: 杂志文章

    doi:10.2217/pgs.09.132

    authors: Funke S,Timofeeva M,Risch A,Hoffmeister M,Stegmaier C,Seiler CM,Brenner H,Chang-Claude J

    更新日期:2010-01-01 00:00:00