Effects of IGF2BP2, KCNQ1 and GCKR polymorphisms on clinical outcome in metastatic gastric cancer treated with EOF regimen.

AIM The present study analyzed Type 2 diabetes mellitus (T2D)-related gene polymorphisms and their impacts on chemotherapeutic response and survival in patients with metastatic gastric cancer (MGC). PATIENTS & METHODS This retrospective study enrolled 108 MGC patients treated with first-line EOF chemotherapy (epirubicin, oxaliplatin and 5-fluorouracil combination chemotherapy). Eleven single nucleotide polymorphisms of five T2D-related genes were determined. RESULTS Among the 11 single nucleotide polymorphisms, three (IGF2BP2 rs4402960, IGF2BP2 rs6769511 and KCNQ1 rs163182) were significantly associated with disease control rate and two (GCKR rs780093 and rs780094) were significantly associated with progression-free and overall survival. CONCLUSION Our results suggest IGF2BP2 and KCNQ1 polymorphisms might be independent predictors of chemotherapeutic response, while GCKR polymorphisms might be independent predictors of survival in MGC patients treated with first-line EOF chemotherapy. Original submitted 30 June 2014; revision submitted 15 April 2015.

[1]  S. Shimoyama.  Diabetes mellitus carries a risk of gastric cancer: a meta-analysis. , 2013, World journal of gastroenterology.

[2]  J. Ajani,et al.  ERCC1 and ERCC2 Variants Predict Survival in Gastric Cancer Patients , 2013, PloS one.

[3]  D. Largaespada,et al.  The role of KCNQ1 in mouse and human gastrointestinal cancers , 2013, Oncogene.

[4]  Yunyu Zhang,et al.  Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies upon the HMGA2-IGF2BP2 pathway. , 2013, Cancer research.

[5]  N. Le,et al.  Genetic Polymorphisms at TIMP3 Are Associated with Survival of Adenocarcinoma of the Gastroesophageal Junction , 2013, PloS one.

[6]  H. Brenner,et al.  Effect of type 2 diabetes predisposing genetic variants on colorectal cancer risk. , 2012, The Journal of clinical endocrinology and metabolism.

[7]  B. Henderson,et al.  Genetic Variants, Prediagnostic Circulating Levels of Insulin-like Growth Factors, Insulin, and Glucose and the Risk of Colorectal Cancer: The Multiethnic Cohort Study , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[8]  M. Pollak.  The insulin and insulin-like growth factor receptor family in neoplasia: an update , 2012, Nature Reviews Cancer.

[9]  K. Anderson,et al.  Genes Related to Diabetes May Be Associated With Pancreatic Cancer in a Population-Based Case-Control Study in Minnesota , 2012, Pancreas.

[10]  K. Moysich,et al.  Diabetes mellitus and gastric carcinoma: Is there an association? , 2011, Journal of carcinogenesis.

[11]  Mark J. Bowser,et al.  IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2. , 2011, Cancer research.

[12]  C. Tseng.  Diabetes conveys a higher risk of gastric cancer mortality despite an age-standardised decreasing trend in the general population in Taiwan , 2010, Gut.

[13]  V. Catalano,et al.  Host genetic variants in the IGF binding protein-3 impact on survival of patients with advanced gastric cancer treated with palliative chemotherapy. , 2010, Pharmacogenomics.

[14]  Tamra E. Meyer,et al.  Diabetes Genes and Prostate Cancer in the Atherosclerosis Risk in Communities Study , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[15]  P. Elliott,et al.  New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk , 2010, Nature Genetics.

[16]  D. Leroith,et al.  Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. , 2010, Cancer research.

[17]  M. Tatematsu,et al.  Gastric carcinogenesis by N‐Methyl‐N‐Nitrosourea is enhanced in db/db diabetic mice , 2009, Cancer science.

[18]  H. Chung,et al.  TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin , 2009, Cancer Chemotherapy and Pharmacology.

[19]  F. Takeuchi,et al.  Confirmation of Multiple Risk Loci and Genetic Impacts by a Genome-Wide Association Study of Type 2 Diabetes in the Japanese Population , 2009, Diabetes.

[20]  M. Kubo,et al.  Hyperglycemia increases risk of gastric cancer posed by Helicobacter pylori infection: a population-based cohort study. , 2009, Gastroenterology.

[21]  Yoon-Koo Kang,et al.  Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[22]  Y. Asmann,et al.  A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer , 2009, Science.

[23]  M. Pollak,et al.  Insulin and insulin-like growth factor signalling in neoplasia , 2008, Nature Reviews Cancer.

[24]  L. Groop,et al.  Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus , 2008, Nature Genetics.

[25]  T. Hansen,et al.  SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations , 2008, Nature Genetics.

[26]  B. Balkau,et al.  The Common P446L Polymorphism in GCKR Inversely Modulates Fasting Glucose and Triglyceride Levels and Reduces Type 2 Diabetes Risk in the DESIR Prospective General French Population , 2008, Diabetes.

[27]  M. McCarthy,et al.  Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes , 2007, Science.

[28]  Edgar Erdfelder,et al.  G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences , 2007, Behavior research methods.

[29]  J. Ajani,et al.  Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Lin He,et al.  SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci , 2005, Cell Research.

[31]  M. Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[32]  A. Norman,et al.  Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer--pooled analysis from three multicenter, randomized, controlled trials using individual patient data. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  Y. Benjamini,et al.  Controlling the false discovery rate in behavior genetics research , 2001, Behavioural Brain Research.

[34]  D. Curtis,et al.  Monte Carlo tests for associations between disease and alleles at highly polymorphic loci , 1995, Annals of human genetics.

[35]  Sung Sook Lee,et al.  Combination chemotherapy with capecitabine (X) and Cisplatin (P) as first line treatment in advanced gastric cancer: experience of 223 patients with prognostic factor analysis. , 2007, Japanese journal of clinical oncology.