Relationship between Glutathione S-Transferase P1 (GSTP1), X-Ray Repair Cross Complementing Group 1 (XRCC1) and 5,10-Methylenetetrahydrofolate Reductase (5,10-MTHFR) Gene Polymorphisms and Response to Chemotherapy in Advanced Gastric Cancer

Background: Our study aimed to investigate the relationship between glutathione S-transferase P1 (GSTP1), 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) and X-ray repair cross complementing group 1 (XRCC1) gene polymorphisms and the response to chemotherapy in advanced gastric cancer. Patients and Methods: 59 cases of advanced gastric cancer were enrolled. All patients were treated with the DCF regimen comprising docetaxel, cisplatin, and 5-fluorouracil. All patients' genotypes regarding GSTP1, XRCC1, and 5,10-MTHFR were analyzed by polymerase chain reaction/ligase detection reaction (PCR-LDR). Results: There were 15 (25.42%) cases of G/G genotype, 21 (35.59%) of G/A genotype, and 23 (38.98%) of A/A genotype for GSTP1, 16 (27.12%) cases of A/A genotype, 18 (30.51%) of G/A genotype, and 25 (42.37%) of G/G genotype for XRCC1, and 21 (35.59%) cases of C/C genotype, 22 (37.29%) of C/T genotype, and 16 (27.12%) of T/T genotype for 5,10-MTHFR. After 2 cycles of chemotherapy, there were 4 cases of complete remission, 14 of partial remission, 19 of stable disease, and 22 of advanced disease, with a total effective rate of 30.51%. Better survival was shown for GSTP1 G/G genotype, XRCC1 A/A genotype, and 5,10-MTHFR T/T genotype (p < 0.05). Conclusion: The gene polymorphisms of GSTP1 G/G, XRCC1 A/A, and 5,10-MTHFR T/T have clinical value for predicting the response to the DCF regimen for advanced gastric cancer.

[1]  Yun Cui,et al.  A meta-analysis of CDH1 C-160A genetic polymorphism and gastric cancer risk. , 2011, DNA and cell biology.

[2]  J. Fleshman,et al.  Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer , 2011, British Journal of Cancer.

[3]  A. Benson,et al.  Refining docetaxel-containing therapy for gastric cancer. , 2011, Gastrointestinal cancer research : GCR.

[4]  Peihua Ni,et al.  X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and gastric cancer risk: A HuGE review and meta-analysis. , 2011, American journal of epidemiology.

[5]  Yoon-Koo Kang,et al.  Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial , 2010, The Lancet.

[6]  Yi-long Wu,et al.  RRM1 single nucleotide polymorphism -37C→A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy , 2010, Journal of hematology & oncology.

[7]  A. Khrunin,et al.  Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients , 2010, The Pharmacogenomics Journal.

[8]  Mu-Kuan Chen,et al.  Glutathione S‐transferase P1 and alpha gene variants; role in susceptibility and tumor size development of oral cancer , 2009, Head & neck.

[9]  C. V. D. Velde,et al.  Gastric cancer – Authors' reply , 2009, The Lancet.

[10]  Herbert Yu,et al.  Glutathione S-transferase polymorphisms and survival in African-American and white colorectal cancer patients. , 2009, Cancer epidemiology.

[11]  Xiang Du,et al.  Polymorphisms in p53, GSTP1 and XRCC1 predict relapse and survival of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy , 2009, Cancer Chemotherapy and Pharmacology.

[12]  B. Henderson,et al.  Urinary Isothiocyanates; Glutathione S-Transferase M1, T1, and P1 Polymorphisms; and Risk of Colorectal Cancer: The Multiethnic Cohort Study , 2009, Cancer Epidemiology Biomarkers & Prevention.

[13]  A. Townsend,et al.  Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin , 2008, Molecular Cancer Therapeutics.

[14]  Wei Zhang,et al.  Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population , 2007, European Journal of Human Genetics.

[15]  S. Larsson,et al.  Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. , 2006, Gastroenterology.

[16]  H. Nagawa,et al.  Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time. , 2006, Cancer letters.

[17]  E. Zintzaras Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis , 2006, Journal of Human Genetics.

[18]  Ling Yang,et al.  Incidence and mortality of gastric cancer in China. , 2006, World journal of gastroenterology.

[19]  C. Wittmer,et al.  Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) – novel predictors for response and survival in gastric cancer patients , 2005, British Journal of Cancer.

[20]  D. Huntsman,et al.  Gastric cancer: New genetic developments , 2005, Journal of surgical oncology.

[21]  J. Robert,et al.  Predicting drug response and toxicity based on gene polymorphisms. , 2005, Critical reviews in oncology/hematology.

[22]  H. Gelderblom,et al.  Pharmacology of oxaliplatin and the use of pharmacogenomics to individualize therapy. , 2005, Cancer treatment reviews.

[23]  N. Magné,et al.  Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients. , 2004, Pharmacogenetics.

[24]  Youngchul Kim,et al.  Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. , 2004, Lung cancer.

[25]  M. Lucock,et al.  Effect of the methylenetetrahydrofolate reductase C677T polymorphism on chemosensitivity of colon and breast cancer cells to 5-fluorouracil and methotrexate. , 2004, Journal of the National Cancer Institute.

[26]  R. Rozen,et al.  Methylenetetrahydrofolate reductase polymorphism in advanced colorectal cancer: a novel genomic predictor of clinical response to fluoropyrimidine-based chemotherapy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[27]  Hongbing Shen,et al.  Polymorphisms of 5,10‐methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: A case‐control study , 2001, International journal of cancer.

[28]  H. Mohrenweiser,et al.  Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair. , 1998, Nucleic acids research.

[29]  D. Rosenblatt,et al.  Methylenetetrahydrofolate reductase. , 2001, Clinical and investigative medicine. Medecine clinique et experimentale.

[30]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[31]  H. Espejo,et al.  [Gastric cancer]. , 1996, Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru.

[32]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.