Dihydropyrimidine dehydrogenases and cytidine‐deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy

Grau, Juan J.; Caballero, Miguel; Monzó, Mariano; Muñoz-García, Carmen; Domingo-Domenech, J.; Navarro, Alfons; Conill, Carlos; Campayo, Marc; Bombí, J.A.

doi:10.1002/jso.21096

Cited by 16 publications

(6 citation statements)

References 16 publications

(19 reference statements)

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“…CDA SNPs did not influence OS in univariable analysis, but the interaction between CDA -31delC SNP and number of first-line chemotherapy cycles significantly influenced OS. In concordance with our results, others did not report any association of this SNP with tumor response, survival [45], and occurrence of treatment-related hematologic toxicity [46].…”

Section: Discussionsupporting

confidence: 93%

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

Erčulj

Kovač

Hmeljak

et al. 2012

Pharmacogenetics and Genomics

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Section: Discussionsupporting

confidence: 93%

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

Erčulj

Kovač

Hmeljak

et al. 2012

Pharmacogenetics and Genomics

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“…In this study estradiol level for patients who received capecitabine was (88.06 ± 15.33) in contrast to another study in Asian countries (Grau et al, 2008) which the mean ± St. Division was 61.51 ± 42.06. In our study, the estradiol level for SNIP rs2072671 for CC (homozygote, mutant type) mean and standard deviation was 41.01±10.78, whereas for AA (homozygote, wild type) it was 51.89±10.42, and for AC (heterozygote type) it was 53.98±10.96.…”

Section: The Genetic Poly Morphism Of Cytidine Deaminase Enzyme In Br...contrasting

confidence: 90%

“…The estradiol level for homozygote AA was the same as heterozygote AC. However, the mutation type of SNIP rs2072671 enzyme CDA, which is responsible for the conversion of capecitabine to 5-FU, lowers the estradiol level, which is in contrast with the study effect chemotherapy that lowers estradiol level (Grau et al, 2008).…”

Section: The Genetic Poly Morphism Of Cytidine Deaminase Enzyme In Br...mentioning

confidence: 86%

Association of Cytidine Deaminase Polymorphism with Capecitabine Effectiveness in Breast Cancer Patients

Aldeen Majeed,

Salih Sahib,

Shakir Mahmood

et al. 2023

Asian Pac J Cancer Prev

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Objective: Cancer is caused by abnormal growth and disruption of homeostatic mechanisms. Breast cancer is a major health problem and the second leading cause of death in women. Capecitabine is a prodrug of 5-fluorouracil, which is a non-cytotoxic agent and is used to treat advanced or metastatic breast cancer. Cytidine deaminase (CDA) plays an important role in the activation of capecitabine by acetylating 5-deoxycytidine in the liver, which ultimately leads to the formation of 5-fluorouracil. In this study, we aimed to investigate the relationship between cytidine deaminase polymorphism and capecitabine efficacy in breast cancer patients. Methods: One hundred breast cancer patients aged 45 to 75 years were included in this study, all of whom received capecitabine as monotherapy. The serum levels of CA15.3, calcium, and estradiol E2 in breast cancer patients were investigated. In addition, the relationship of these markers with cytidine deaminase polymorphism was investigated in order to show the association of cytidine deaminase polymorphism with capecitabine efficacy in breast cancer patients. Result: The findings of this study showed that there is a statistically significant relationship between CDA enzyme polymorphisms (rs2072671 and rs532545) with estradiol and CA15.3 serum levels and a non-significant relationship with calcium level. Furthermore, patients who participated were highly polymorphic and heterozygotes genotypes had the highest frequency in both rs2072671 and rs532545 polymorphisms. Conclusion: The results obtained from the present study identified different genetic polymorphisms in the gene encoding the CDA enzyme. Overall, our results clearly showed direct evidence for the association of cytidine deaminase polymorphism with the efficacy of capecitabine in breast cancer patients, which could be useful in reducing side effects and improving drug response to capecitabine.

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“…A study conducted by Grau et al . [ 79 ] investigated the role of genetic variations in DPYD in place of looking at DPD expression, analyzing the prognostic value of genetic single nucleotide polymorphisms (SNPs) of intratumoral DPYD and CDA (cytidine-deaminase enzyme, which can influence the activity of TS) in patients with GC treated with adjuvant fluoropyrimidine (tegafur). SNP of DPYD 1 (A/G; Ile453Val) was associated with better survival while the SNP (C/T; Arg29Cys) of DPYD 2 showed a benefit in terms of relapse and survival if associated with the polymorphism of CDA (A/C; Lys27Gln) [ 79 ] .…”

Section: Impact Of Dpd Expression In Different Cancer Typesmentioning

confidence: 99%

Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase

Merloni¹,

Ranallo²,

Scortichini³

et al. 2019

CDR

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Fluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (Clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy.

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Dihydropyrimidine dehydrogenases and cytidine‐deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy

Abstract: Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.

Cited by 16 publications

References 16 publications

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

Association of Cytidine Deaminase Polymorphism with Capecitabine Effectiveness in Breast Cancer Patients

Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase

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