1.Study on the Relationship between UGT1A1 Gene Polymorphisms and Irinotecan-induced ADR
Yunhong YOU ; Songping WANG ; Chao ZHU ; Jie CHAI
China Pharmacy 2016;27(5):638-641
OBJECTIVE:To study the correlation of UGT1A1 gene polymorphisms with the incidence and severity of irinote-can-associated ADR in the patients with irinotecan-based chemotherapy. METHODS:56 patients with advanced gastroenteric tumor and small cell lung carcinoma were selected from our hospital and treated with irinotecan-based chemotherapy. The occurrence of ADR was observed during chemotherapy. Gene DNA were collected from peripheral blood sample,and UGT1A1 gene polymor-phisms was determined. The relationship of genotypes with ADR was analyzed. RESULTS:TA sequence of UGT1A1*28 genetic lo-cus was as follows:wild-type genotype TA6/6(42 cases,75.0%),heterozygous mutation-type TA6/7(13 cases,23.2%)and ho-mozygous mutation-type TA7/7(1 cases,1.8%);that of UGT1A1*6 genetic locus was as follows:wild-type genotype(44 cases, 78.6%),heterozygous mutation-type(10 cases,17.9%)and homozygous mutation-type(2 cases,3.6%). In UGT1A1*28 genetic locus,6 wild-type genotype patients and 3 mutation-type patients suffered from Ⅲ degree or above hypoleukemia and/or neutrope-nia (14.3% vs. 21.4%,P>0.01),among which only one homozygous mutation-type patient suffered from hypoleukemia and/or neutropenia(100%);6 wild-type genotype patients and 2 mutation-type patients suffered from Ⅲ degree or above diarrhea(14.3%vs. 14.3%,P>0.01),among which only one homozygous mutation-type patient suffered from Ⅲ degree or above diarrhea (100%). In UGT1A1*6 genetic locus,3 wild-type genotype patients and 8 mutation-type patients suffered from Ⅲ degree or above neutropenia (6.8% vs. 66.6%,P<0.01),and 2 wild-type genotype patients and 7 mutation-type patients suffered from Ⅲ degree or above diarrhea(4.5% vs. 58.3%,P<0.01). CONCLUSIONS:Among patients with advanced gastroenteric tumor and small cell lung carcinoma,UGT1A1 gene wild-type gene promoter is most common,followed by heterozygous mutation-type,and homozy-gous mutant rare. For TA7/7 homozygous mutation-type patients,irinotecan-based chemotherapy increase the risk of Ⅲ degree or above hypoleukemia and/or neutropenia and diarrhea. For TA6/7 heterozygotes patients and TA6/6 wild-type patients, irinote-can-based chemotherapy doesn't affect the incidence of Ⅲ degree or above neutropenia and diarrhea. For UGT1A1*6 genetic locus mutation-type patients,irinotecan-based chemotherapy significantly increase the risk of Ⅲ degree or above neutropenia and diar-rhea.
2.Changes of serum CRP and hs-CRP levels in patients with liver cancer and depression and their influence on prognosis
Fengjuan ZHAO ; Qi WANG ; Yunhong REN ; Jueling WEI ; Lequn LI ; Xinhua ZHAO ; Juan TANG ; Xuemei YOU
Practical Oncology Journal 2019;33(1):27-33
Objective The objective of this study was to investigate the effect of depression on serum levels of C-reactive protein(CRP)and high-sensitivity C-reactive protein(hs-CRP),and prognosis in liver cancer patients. Methods A total of 251 patients with liver cancer undergoing hepatectomy were enrolled. The hospital anxiety and depression scale( HADS-D) and 9-item patients health questionnaire(PHQ9) were assessed for depression before 3 days for surgery. Patients were divided into depression group(n=95)and non-depression group(n=156) according to the scores. Preoperative serum levels of CRP,hs-CRP,ALT and AST were measured and compared between the depression and non-depression groups. Survival analysis Kaplan-Meier method was used to compare the disease-free survival(DFS)and total survival(OS)between the two groups. Results The serum levels of CRP, hs-CRP,ALT and AST in the depression group were significantly higher than those in the non-depression group(P<0. 05). The follow-up of 3. 5-year showed that 164 patients(65 in depression group and 99 in non-depression group)had recurrence or metas-tasis and 47 patients(22 in depression group and 25 in non-depression group) died. The DFS and OS in the depression group were significantly lower than those in the non-depression group(P< 0. 05). Cox multiple regression analysis showed that liver function grading,BCLC staging and depression were independent risk factors for the prognosis of liver cancer. Spearman correlation analysis showed that patients′degree of depression was positively correlated with serum levels of CRP and hs-CRP(P<0. 05),DFS and OS were negatively correlated with serum levels of CRP and hs-CRP(P<0. 05). Conclusion Depression may mediate elevated serum levels of CRP and hs-CRP,maintain inflammatory response in patients,lead to increased liver function damage,elevate levels of ALT and AST,and thus adversely affect the prognosis of patients with liver cancer.