Genetic polymorphisms of GSTP1 related to response to 5-FU-oxaliplatin-based chemotherapy and clinical outcome in advanced colorectal cancer patients.
OBJECTIVE
To determine whether genetic polymorphisms of GSTP1 Ile105Val (A-->G) predict chemosensitivity and clinical outcome in patients with advanced colorectal cancer, treated by 5-FU/oxaliplatin-based chemotherapy.


METHODS
In this retrospective study, the population consisted of 122 advanced colorectal cancer patients (III stage 51, IV stage 71). Patients were treated with 5-FU-oxaliplatin-based chemotherapy, and their response was evaluated after at least two cycles of treatments; all patients (122) were evaluated for median survival time (MST). GSTP1 genotypes were detected by TaqMan-MGB probe methods.


RESULTS
75 patients (61.47%) were Ile/Ile genotype, 10 (8.2%) were Val/Val genotype, and 37 (30.33%) were Ile/Val genotype. Patients possessing the glutathione S-transferase P1-105 Val/Val genotype showed a response rate of 60.0% compared to 25.89% in patients harboring at least one GSTP1-105 Ile allele (p = 0.032). GSTP1-105 Val/Val patients demonstrated a significant superior median survival time of 20.4 months (95% CI: 11.85 to 28.95) compared to 6.5 months (95% CI: 4.26 to 8.74) in patients with 105 Ile/Ile genotype and 10.3 months (95% CI: 7.05 to 13.55; p <0.01) in patients with GSTP1 105 Ile/Val genotype.


CONCLUSIONS
The GSTP1 105Val/105Val genotype is associated with a higher clinical response rate to oxaliplatin-based chemotherapy and with increased survival of patients with advanced colo-rectal cancer, receiving 5-FU/oxaliplatin chemotherapy.
Jun
Liang
L
Department of Oncology, The Affiliated Hospital of Medical College, Qing Dao University, Quingdao, China. yry0303@yahoo.com.cn
Haiping
Zhang
Z
Beibei
Yin
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D051549:Glutathione S-Transferase pi; D005472:Fluorouracil