Abstract
BackgroundAddictions 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.ResultsLiterature 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.ConlusionsCancer 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0167-x) contains supplementary material, which is available to authorized users.
Highlights
Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders
Nicotinic acetylcholine receptor genes were widely explored for alcohol and nicotine addiction [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]
The primary aims of this study were to determine whether there exists a genetic basis to the relationship between smoking, alcohol, and opioid addiction, and to identify candidate genes associated with the three phenotypes for further study
Summary
Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Several clinical trials found that patients with a history of cigarette smoking and illicit drug abuse had a significantly higher risk for opioid addiction than those without the history [8,9,10,11]. Taken together, these studies suggest that past addictive behaviors to various substances may predict opioid addiction in cancer patients with opioid prescriptions for pain. Very few studies have explored whether there exists a genetic basis and common
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