Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab

Single-nucleotide polymorphisms (SNPs) related to hereditary thrombophilia were investigated as risk factors for thromboembolism in cancer patients. Their effect in metastatic colorectal cancer (mCRC) has never been explored so far. Our aim was to analyse the effect of coagulation factor V (FVL G169...

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Bibliographic Details
Published in:The pharmacogenomics journal 2017-07, Vol.17 (4), p.331-336
Main Authors: Falvella, F S, Cremolini, C, Miceli, R, Nichetti, F, Cheli, S, Antoniotti, C, Infante, G, Martinetti, A, Marmorino, F, Sottotetti, E, Berenato, R, Caporale, M, Colombo, A, de Braud, F, Di Bartolomeo, M, Clementi, E, Loupakis, F, Pietrantonio, F
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Allelomorphism
Analysis
Bevacizumab
Bevacizumab - therapeutic use
Blood proteins
Cancer
Cancer metastasis
Cancer patients
Care and treatment
Chemotherapy
Coagulation
Coagulation factors
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Deoxyribonucleic acid
DNA
Dosage and administration
Drug therapy
Factor V
Factor V - genetics
Female
Genetic aspects
Genetic Predisposition to Disease - genetics
Genotype
Genotypes
Health aspects
Health risks
Humans
Identification and classification
Immunotherapy
Male
Metastases
Metastasis
Methods
Methylenetetrahydrofolate reductase
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Middle Aged
Monoclonal antibodies
Obesity
Patients
Peripheral blood
Plasminogen Activator Inhibitor 1 - genetics
Plasminogen activator inhibitors
Platelets
Polyamide-imides
Polymerase chain reaction
Polymorphism
Polymorphism, Single Nucleotide - genetics
Properties
Prospective Studies
Prothrombin
Prothrombin - genetics
Risk
Risk factors
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Targeted cancer therapy
Thromboembolism
Thromboembolism - genetics
Thrombophilia
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Summary:Single-nucleotide polymorphisms (SNPs) related to hereditary thrombophilia were investigated as risk factors for thromboembolism in cancer patients. Their effect in metastatic colorectal cancer (mCRC) has never been explored so far. Our aim was to analyse the effect of coagulation factor V (FVL G1691A), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and plasminogen activator inhibitor type 1 (PAI-1 5G/4G) allelic variants in this setting. Fifty-two patients treated with first-line chemotherapy plus bevacizumab who developed a thromboembolic event in their lifetime were initially genotyped. A contemporary cohort of 127 patients who did not experience any thromboembolic event was also analysed. DNA was extracted from peripheral blood and genotypes were determined by real-time PCR, using LightSNiP (TIB MOLBIOL) on LightCcler 480 (Roche). The association between thromboembolism and SNPs was investigated by univariable and multivariable analyses. All SNPs were in Hardy-Weinberg equilibrium (χ test P>0.20). FVL G1691A and PT G20210A were present only in heterozygosis in 4 (2.2%) and 7 (3.9%) patients, respectively; MTHFR C677T in homozygosis in 29 (16.2%), MTHFR A1298C in homozygosis in 13 (7.3%); PAI-1 5G/4G in 98 (54.7%) and 4G/4G in 41 (23%) patients. At univariable analysis, treatment duration was significantly associated with thromboembolism (P
ISSN:1470-269X
1473-1150
DOI:10.1038/tpj.2016.22