结直肠癌dpyd、mthfr基因多态性与5-fu化疗相关毒性的研究-study on the relationship between polymorphism of dpyd and mth fr gene and chemotherapy-related toxicity of 5 - fu in colorectal cancer.docx

The polymorphism of DPYD and MTHFR Gene with 5-FU related-toxicity in Colorectal CancerAbstractThe polymorphism of DPYD and MTHFR Gene with 5-FU related-toxicity in Colorectal CancerAbstractObject: To investigate the polymorphism of DPYD and MTHFR gene of patients with CRC(colorectal cancer) , to observe the relationship between polymorphism of two genes and 5-FU toxicity, and then to provide some genetic basis for predicting curative or adverse effects of 5-FU-based chemotherapy, as guidelines for better clinical treatment.Methods: (1).Venous blood samples from 60 CRC patients diagnosis with surgical treatment and pathological test at the First Affiliated Hospital of Suzhou University were collected between March,2011 and March,2012. All patients were administered 5-FU-based regimen as postoperative adjuvant chemotherapy after ECOG system [1]assessment(?2scores), as well as the average chemotherapy cycle for 4~6.(2). To detect the polymorphism of the exon 14 of DPYD gene and MTHFR C677T after serial procedures such as blood samples EDTA anticoagulant, genomic DNA extraction, polymerase chain reaction (PCR) amplification, gene sequencing and so forth.(3). All the patients got accurate ECOG system assessment(?2scores) and image examination(X-ray,CT scan, B ultrasound) as well as RT(regular blood test), whole biochemistry set, mainly hepatorenal function when every chemotherapy cycle started. The average interval between two chemotherapy cycles is about 4 weeks. During the period, 60 patients received reviews of RT and hepatorenal functions set at outpatient every 2 weeks. To evaluate 5-FU toxicity combination with clinical profile in accordance with WHO scale; to find out the relationship between the polymorphism of two genes(DPYD,MTHFR)and 5-FU adverse effect.Results:(1). The DPYD genes Exon14 IVSl4 + l sites are wholly G /G wild-type, while the other gene types ( GA,AA) were not detected , which could lead to 5-FU-related-toxicity.(2). Of all 60 patients, the propo