RESUMEN
Background Early relapse in colorectal cancer (CRC) after curative resection is mainly attributed to the key determinants such as tumor histology, stage, lymphovascular invasion, and the response to chemotherapy. Case presentation Interindividual variability in the efficacy of adjuvant chemotherapy between patients receiving the same treatment may be ascribed to the patients' genetic profile. In this report, we highlight a clinical case of a patient with stage II CRC who relapsed within a short period after starting adjuvant chemotherapy and was later found to have multiple genetic polymorphisms in the DPYD, TYMS, MTHFR, and DHFR genes. Conclusions Based on the clinical data of the patient and the key role of these genes in 5-fluorouracil pathway, we hypothesize that these variants may contribute to the drug response and early relapse in CRC.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fluorouracilo/uso terapéutico , Recurrencia Local de Neoplasia/genética , Polimorfismo Genético , Antimetabolitos Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/cirugía , Dihidrouracilo Deshidrogenasa (NADP)/genética , Femenino , Fluorouracilo/administración & dosificación , Ácido Fólico/metabolismo , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Pruebas de Farmacogenómica , Tetrahidrofolato Deshidrogenasa/genética , Timidilato Sintasa/genéticaRESUMEN
BACKGROUND: Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS: The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS: Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.