Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer.

Abstract

BACKGROUND:

Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens.

MATERIALS AND METHODS:

DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents).

RESULTS:

There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A+high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05).

CONCLUSIONS:

Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

• Authors: Zhi-Jun Yuan, Wen-Wu Zhou, Wei Liu, Bai-Ping Wu, Jin Zhao, Wei Wu, Yi He, Shuo Yang, Jing Su, Yi Luo
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 16 Issue 10 Pg. 4347-51 ( 2015) ISSN: 2476-762X [Electronic] Thailand
• PMID: 26028097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Tumor Suppressor Proteins
• Deoxycytidine
• RRM1 protein, human
• Ribonucleoside Diphosphate Reductase
• GSTP1 protein, human
• Glutathione S-Transferase pi
• Cisplatin
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• China
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Resistance, Neoplasm (genetics)
• Female
• Genotype
• Glutathione S-Transferase pi (genetics)
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Response Evaluation Criteria in Solid Tumors
• Ribonucleoside Diphosphate Reductase
• Tumor Suppressor Proteins (genetics)
• Gemcitabine