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Genetic variants in the glutathione S-transferase genes and survival in colorectal cancer patients after chemotherapy and differences according to treatment with oxaliplatin

Kap, Elisabeth J.a; Richter, Swantjea; Rudolph, Anjaa; Jansen, Linab; Ulrich, Alexisc; Hoffmeister, Michaelb; Ulrich, Cornelia M.d,e; Brenner, Hermannb; Chang-Claude, Jennya

Pharmacogenetics and Genomics: July 2014 - Volume 24 - Issue 7 - p 340–347
doi: 10.1097/FPC.0000000000000059
ORIGINAL ARTICLES
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Introduction The glutathione S-transferase (GST) enzymes are involved in the detoxification of a range of carcinogenic compounds as well as chemotherapeutic agents. Therefore, genetic variants in the GST genes could influence survival in patients with colorectal cancer (CRC). Results from previous studies have been inconsistent and therefore we investigated the association between the GSTP1 ile105val polymorphism and the copy number variants of the GSTM1 and GSTT1 genes and survival in CRC patients treated with adjuvant/palliative chemotherapy.

Patients and methods We included 755 CRC patients with stage II–IV disease from two population-based studies carried out in Germany. Genotyping of the GSTP1 polymorphism was carried out using fluorescence-based melting curve analysis and copy number variants were determined using a multiplex PCR. Survival analysis was carried out using the Cox regression model, adjusting for age, sex, UICC stage, cancer site, and radiation therapy.

Results Compared with noncarriers, CRC patients who were homozygote carriers of GSTM1 had significantly poorer survival after treatment with oxaliplatin [hazard ratio (HR) 2.25, 95% confidence interval (CI) 0.93–5.44] than those not treated with oxaliplatin (HR 0.64, 95% CI 0.30–1.34; P for heterogeneity=0.031). The association was significant in metastatic CRC patients treated with oxaliplatin (HR 3.59, 95% CI 1.29–10.03). Neither the GSTP1 105val allele nor the GSTT1 deletion was significantly associated with CRC survival.

Conclusion Our data suggest that GSTM1 may be a predictive marker for oxaliplatin therapy; however, independent large studies are warranted to confirm these results.

aDivision of Cancer Epidemiology, German Cancer Research Center

bDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center

cDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University of Heidelberg

dDivision of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany

eCancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Correspondence to Prof. Dr. Jenny Chang-Claude, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany Tel: +49 6221 422373; fax: +49 6221 422203; e-mail: j.chang-claude@dkfz-heidelberg.de

Received January 14, 2014

Accepted April 13, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins