Fluoropyrimidine-Associated Toxicity in Two Gastrointestinal Cancer Patients: Potential Role of Common DPYD Polymorphisms.

نویسندگان

  • Felicia Stefania Falvella
  • Marco Luoni
  • Stefania Cheli
  • Sergio Fava
  • Massimiliano Cergnul
چکیده

While the majority of patients can be treated safely with fluoropyrimidine, some experience severe fluoropyrimidine-associated toxicity. The frequency and severity of these adverse events vary from patient to patient and are partially explained by genetic polymorphism into the dihydropyrimidine dehydrogenase (DPYD) gene. Carriers of the rare allelic variants DPYD*2A, DPYD*13, and DPYD D949V are more likely to experience severe adverse reactions during fluoropyrimidine-based therapy. However, these 3 genetic variants explain only a small percentage of the overall drug toxicity, and more frequent ones such as homozygous or compound heterozygous DPYD V732I can play a key role.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Personalized Medicine and Imaging Polymorphisms in MIR27A Associated with Early-Onset Toxicity in Fluoropyrimidine-Based Chemotherapy

Purpose: ThemicroRNAmiR-27awas recently shown to directly regulate dihydropyrimidine dehydrogenase (DPD), the key enzyme in fluoropyrimidine catabolism. A common polymorphism (rs895819A>G) in themiR-27a genomic region (MIR27A) was associated with reduced DPD activity in healthy volunteers, but the clinical relevance of this effect is still unknown. Here, we assessed the association of MIR27A ge...

متن کامل

Polymorphisms in MIR27A Associated with Early-Onset Toxicity in Fluoropyrimidine-Based Chemotherapy.

PURPOSE The microRNA miR-27a was recently shown to directly regulate dihydropyrimidine dehydrogenase (DPD), the key enzyme in fluoropyrimidine catabolism. A common polymorphism (rs895819A>G) in the miR-27a genomic region (MIR27A) was associated with reduced DPD activity in healthy volunteers, but the clinical relevance of this effect is still unknown. Here, we assessed the association of MIR27A...

متن کامل

Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on prognosis of breast cancer patients with chemotherapy

Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD p...

متن کامل

Undetected Toxicity Risk in Pharmacogenetic Testing for Dihydropyrimidine Dehydrogenase

Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%-30% of patients. Dihydropyrimidine dehydrogenase (DPD), a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene (DPYD) polymorphisms are a...

متن کامل

Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

OBJECTIVE Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising app...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Chemotherapy

دوره 62 5  شماره 

صفحات  -

تاریخ انتشار 2017