Study On The Relationship Between DPYD Gene And Prognosis In Breast Cancer Receiving 5-FU Chemotherapy

Objectives: Dihydropyrimidine dehydrogenase (DPD) plays an essential role in thecatabolism of 5-fluorouracil (5-FU) used in breast cancer therapy. The purpose of thisstudy was to determine DPD mRNA expression levels in normal breast tissues, primarybreast cancer tissues and lymph node metastatic tissues, to determine the relationshipbetween DPYD gene expression levels and clinicopathological features and to evaluateits prognostic significance in breast cancer patients receiving 5-FU chemotherapy.Method: Primary breast cancer specimens were obtained from 108 patients who hadundergone surgery at Tianjin Cancer Hospital between January 2002 and October 2003.DPD mRNA level assessed by real-time RT-PCR in 108 primary breast cancer tissues,paired 30 breast cancer tissues and adjacent normal breast tissues, matched 30 breastcancer tissues and lymph node metastatic tissues was to determine the relationshipbetween DPD mRNA expression and clinical parameters such as age, clinical stage,pathological tumor size, pathological lymph node status, positive lymph node,histological grade, ER status, PR status and Her-2 status; and its correlation withprognosis in breast cancer patients receiving 5-FU chemotherapy.Results:1. DPD mRNA expression levels in primary breast cancer tissues were 82% lower thanin normal breast tissues, the difference was significant (p=0.001), we conclude thatDPD mRNA expression levels were down-regulation in primary breast cancer tissues;DPD mRNA expression levels in primary breast cancer tissues were 29% lower than inlymph nodes metastatic tissues, the difference was significant (p=0.019), and we got theresults that DPD mRNA expression levels were up-regulation in lymph nodes metastatictissues.2. DPD mRNA expression in primary breast cancer tissues were lower than in normalbreast tissues, the difference was significant (p=0.000); DPD mRNA expression in lymph node metastatic tissues were almost the same in primary breast cancer tissues(p＞0.05).3. DPD mRNA expression was significantly lower in clinical stageⅢorⅣthan instageⅠorⅡ, and the difference was significant (p=0.048); DPD mRNA wassignificantly lower in lymph-node involvement patients than patients with lymphnode-negative, and the difference was significant (p=0.012); DPD mRNA expressionwas significantly lower in gradingⅢthan in gradingⅠorⅡ, and the difference wassignificant (p=0.048).4. When the cutoff of DPD mRNA expression was set at 6.90E-03, patients with ageless than 50 years old receiving 5-FU or 5-FU derivatives chemotherapy, the low DPDgroup had better DFS than the high group ,and the difference was significant (p=0.035);patients with negative clinical lymph node receiving 5-FU or 5-FU derivativeschemotherapy, the low DPD group had better DFS than the high group, and thedifference was significant (p=0.047); patients with stageⅠorⅡand tumor size smallerthan 5 cm receiving 5-FU or 5-FU derivatives chemotherapy, the low DPD group hadbetter DFS than the high group, but there was no significant difference (p=0.06 and p=0.09, separately).5. For patients with advanced stage and histological gradeⅢ, we compared DPDmRNA expression in patients with and without preoperative 5-FU or 5-FU derivativeschemotherapy, we found that with 5-FU group was significant higher than without 5-FUgroup (p=0.024 and p=0.034, separately). We concluded that DPD mRNA level wasinduced by preoperative 5-FU or 5-FU derivatives chemotherapy.Conclusion: DPD mRNA expression levels were down-regulation in primary breastcancer tissues, and DPD mRNA expression levels were up-regulation in lymph nodesmetastatic tissues; DPD mRNA expression was significantly lower in primary breastcancer tissues than in normal breast tissues, DPD mRNA expression in lymph nodemetastatic tissues were almost the same in primary breast cancer tissues; DPD mRNAexpression was down-regulation in progression of breast cancer; For the patients younger than 50 years old and negative clinical lymph node receiving 5- FU or 5-FUderivatives, DPD mRNA level down-regulation predict a significantly better prognosis;5-FU or 5-FU derivatives chemotherapy may induce DPD mRNA expression inadvanced stage and histological gradeⅢpatients.