EffectofGSTP1geneticvariationontherecurrenceriskandprognosisofcolorectal cancerpatients received postoperative adjuvant chemotherapy
10.3872/j.issn.1007-385x.2020.04.013
- VernacularTitle:GSTP1基因遗传变异对结直肠癌患者术后接受辅助化疗的复发风险及 预后的影响
- Author:
ZHENG Xiaoyong
1
,
2
;
BAI Yan
3
,
4
;
YANG Yage
1
,
2
;
GUO Changqing
5
,
6
Author Information
1. 1.Department of Gastroenterology,theThird Provincial People'
2. s Hospital of Henan Province, Zhengzhou 450006, Henan, China
3. 2. Department of Gastroenterology, the First people'
4. s Hospital of Zhengzhou, Zhengzhou 450004, Henan, China
5.
6. 3.DepartmentofGastroenterology,theFirstAffiliatedHospitalofZhengzhou University, Zhengzhou 450052, Henan, China
- Publication Type:Journal Article
- Keywords:
colorectal cancer (CRC);
adjuvant chemotherapy;
glutathioneS-transferase P-1 (GSTP1);
polymorphism;
genetic variation;
recurrence;
prognosis
- From:
Chinese Journal of Cancer Biotherapy
2020;27(4):420-426
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To investigate the influence of glutathione S-transferase P-1 (GSTP1) genetic variation on the recurrence risk and prognosis of colorectal cancer (CRC) patients received postoperative adjuvant chemotherapy. Methods: The clinical data of 195 CRC patients, who received postoperative adjuvant chemotherapy in the Department of Gastroenterology of the FirstAffiliated Hospital of Zhengzhou University from January 2010 to December 2018, were collected for this study. 5-fluorouracil (5-FU) based adjuvant chemotherapy was given after surgical resection. The recurrence status of the patients was assessed during hospitalization period, and the long-term survival data of patients were obtained by telephone follow-up after finishing the scheduled adjuvant chemotherapy. GSTP1 genotyping was performed with the DNA extracted from peripheral blood specimens, and its correlation with patients’clinical characteristics wasanalyzed.Additionally, RNAwasextractedfrom peripheral blood mononuclear cell (PBMC) specimens of some CRC patients that prior to chemotherapy for GSTP1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and adjusted by multivariate Cox regression model. Results: The median disease-free survival (DFS) of the 195 CRC patients was 4.8 years, and the median overall survival (OS) was 6.2 years. Polymorphism analysis indicated that the I105VlocusofGSTP-1coding region was correlated with prognosis. The prevalence of I105V in the study population: AA genotype of 135 cases (69.23%), AG genotype of 56 cases (28.72%) and GG genotype of 4 cases (2.05%), the minor allele frequency of I105V was 0.16. The genotype distribution was in accordance with Hardy-Weinberg equilibrium (P>0.05). The analysis of recurrence risk and prognosis found that the median DFS of patients with AA genotype and AG/GG genotype was 5.7 and 3.9 years respectively (P<0.01), while the median OS of two groups of patients was 7.0 and 4.5 years respectively (P<0.01). The multivariate Cox regression results indicated that AG/GG genotype was an independent factor for OS (OR=1.54, P<0.05). The mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes were significantly higher than those patients with AA genotype (P<0.01). Conclusion: GSTP1 I105V genetic variation influences the recurrence risk and prognosis of CRC patients received postoperative adjuvant chemotherapy possibly via mediating the mRNAexpression of GSTP1.
- Full text:20200413.pdf
