The Detection And Clinical Significance Of DPYD、 MTHFR Gene Polymorphism In Colorectal Cancer

Objcet: To investigate the DPYD、MTHFR gene polymorphism in the colorectalcancer(CRC)，to provide the information for5-FU treatment，find the relationshipbetween the MTHFR gene polymorphism and clinical pathological factors of CRC，and toprovide some theoretical basis for establishing a simple,rapid and economical method oftesting gene status in the clinical practice.Methods: Took52cases of postoperative tumor tissues and normal tissues ofcolorectal cancer patients with surgical treatment as experimental materials, which werefrom the First Affiliated Hospital of Suzhou University in March to July of2011. the tumortissues fixed in neutral formalin,dehydrated,soaked and embedded in paraffin,tumor tissuesDNA was extracted with the method of manual microdissection and DNA extraction kit forparaffin specimen, while all the normal tissues DNA was extracted directly by grinded andhomogenated. After the experimental steps of polymerase chain reaction (PCR)amplification, sequencing, the exon13、14of DPYD gene and Codon677of the MTHFRgene polymorphism were identified and analyzed with the corresponding clinicalpathological data.Results:（1）The DPYD Genes Exon14IVSl4+l sites are all of G/G wild-type,while G/A and A/A which can cause the5-FU-related-toxicity was not detected in52colorectal cancer tumors and normal tissues.（2）Only one case of T/G detected in DPYD gene Exon13c.1679site, the others areT/T wild-type.（3）MTHFR667site gene polymorphism distribution, T/T was5cases (9.6%), C/Twas26cases (50%), C/C wild-type was21cases(40.4%) in tumor tissue, while in normaltissue, T/T was11cases(21.2%), C/T was26cases (50%), C/C wild-type was15cases (28.8%), T/T gene type in the normal tissue was significantly higher than the tumor tissue,but the difference is not statistically significant (P>0.05).（4）MTHFR667site gene polymorphism distribution has no significant correlationwith the pathological histological types,location of tumors,clinical stage, or with lymphnodes or remote metastasis in CRC. But T/T genotype distribution in over60years oldpatients was significantly higher than the other age of patients, the difference wasstatistically significant (P <0.05).Conclusion:（1）The DPYD gene Exon14IVSl4+l G> A mutation in the Chinesepopulation is0%, the polymorphism distribution of DPYD gene Exon14in Chinese wasG/G genotype，so the distribution have the ethnic and geographical differences.（2）The DPYD gene Exon13c.1679T> G mutation was not the hot spot mutations inChina.（3）MTHFR gene677site gene polymorphism is associated with colorectalcancer,the T/T genotype may reduce the risk of colorectal cancer,sample cases should beexpand for further study.（4）MTHFR667site gene polymorphism distribution,T/T genotype distribution inover60years old patients was significantly higher than the other age of patients, thedifference was statistically significant (P <0.05). but the polymorphism distribution has nosignificant correlation with other clinical pathological factors, it should be expand forfurther study.