Frequência genotípica em amostras de MTHFR para o polimorfismo C677T em pacientes da cidade de Curitiba-PR

Herkenhoff, Marcos Edgar; Backes, Rodrigo Guilherme; Gaulke, Rodrigo; Remualdo, Vanessa Rosália

doi:10.1590/s1676-24442012000600008

Cited by 1 publication

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References 17 publications

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“…Considerando as frequências alélicas das variantes em MTHFR estudadas, obtivemos entre os pacientes deste trabalho 62,89% apresentando o alelo variante T na posição 677 (rs1801133) e 35,71% apresentando o alelo C na posição 1298 (rs1801131). Estes achados são similares aos de estudos nacionais realizados nas regiões Sul e Sudeste (217)(218)(219)(220). Em contrapartida, há diferenças entre as incidências de homozigotos e heterozigotos para estas variantes em trabalhos desenvolvidos no Nordeste brasileiro.…”

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Caracterização farmacoepidemiológica dos pacientes em tratamento com capecitabina

da Costa Duarte

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Colorectal cancer is the third most prevalent neoplasm worldwide ahead of gastric cancer, which is in the fifth position. Among the therapeutic options available for these neoplasms, capecitabine, which may be prescribed combined or not with other chemotherapic drugs, is noteworthy. It is an oral antineoplastic that, despite its high efficacy, has important toxicities associated with its use, and may be dose-limiting with a significant impact on patients' quality of life. The aim of this study was to evaluate the incidence of major toxicities in patients using capecitabine for the treatment of gastric and colorectal cancer and to correlate them with the presence of variants in the DPYD and MTHFR genes that are involved in important steps of the mechanism of action of this chemotherapeutic. This was an analytical, observational cohort study. Gastrointestinal, hematological, renal, dermatological, neurological, hepatic and fatigue toxicities were evaluated. The severity of these events was classified by the Common Toxicity Criteria for Adverse Events (version 4.0). The quality of life of the patient was also evaluated before the start of chemotherapy and after the third cycle of treatment through general and specific questionnaires for the type of cancer developed by the European Organization for Research and Treatment of Cancer and validated for Portuguese language. Adherence to treatment and knowledge of therapy were assessed using Morisky-Green and MedTake. Patients were genotyped for the following genetic variants by the real-time PCR technique: DPYD*5 (1627A> G), DPYD*9A (85T>C), MTHFR 677C>T and MTHFR 1298A>C. A total of 109 patients (58.61 ± 10.74 years, 51.38% male) were included, and the most frequent toxicities were: nausea, among those of gastrointestinal order; anemia, among those of hematological order; hand-foot syndrome among those of dermatologic order; paresthesia among those of neurological order and fatigue. Regarding general quality of life, there was a significant improvement in the "social function" and "pain" domains after the third treatment cycle. The majority of patients had high adherence to capecitabine and the level of knowledge regarding treatment improved significantly between patients over the first three treatment cycles. The DPYD*5 variant was correlated with an increase in non-clinically significant creatinine and a lower incidence of dysgeusia among patients, DPYD*9A with a decrease in non-clinically significant serum hemoglobin and a higher incidence of diarrhea and MTHFR 677C>T was associated with lymphopenia among study participants. Further studies need to be conducted in a larger group of patients to better assess the potential of these genetic variants in the pre-treatment screening for prevention of severe toxicities induced by capecitabine.

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Section: Discussionunclassified

Caracterização farmacoepidemiológica dos pacientes em tratamento com capecitabina

da Costa Duarte

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Frequência genotípica em amostras de MTHFR para o polimorfismo C677T em pacientes da cidade de Curitiba-PR

Cited by 1 publication

References 17 publications

Caracterização farmacoepidemiológica dos pacientes em tratamento com capecitabina

Caracterização farmacoepidemiológica dos pacientes em tratamento com capecitabina

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