title: Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.
abstract: BACKGROUND
  Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction.
  
  
  RESULTS
  Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling.
  
  
  CONCLUSIONS
  Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.
authors.affiliation: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. creyes@mdanderson.org.
authors.forename: Cielito C
authors.initials: CC
authors.lastname: Reyes-Gibby
authors.affiliation: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. cyuan95@yahoo.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jianwang@mdanderson.org.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. syeung@mdanderson.org.
authors.forename: Sai-Ching J
authors.initials: SC
authors.lastname: Yeung
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. sshete@mdanderson.org.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019295:Computational Biology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics*; D053263:Gene Regulatory Networks; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics; D009293:Opioid-Related Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000276:immunology*; D012907:Smoking / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D005819:Genetic Markers; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3