One SNP linked to two diseases-addiction and cancer: a double whammy? Nicotine addiction and lung cancer susceptibility.
- Authors
- Volkow, N; Rutter, J; Pollock, J D; Shurtleff, D; Baler, R
- Year
- 2008
- Journal
- Molecular psychiatry
- PMID
- 18936755
- DOI
- 10.1038/mp.2008.71
- PMCID
- PMC4827504
Convergent evidence has established that a polymorphism in the α3/α5/β4 nicotinic receptor subunits cluster is associated with increased risk of nicotine dependence (ND) and of two of its most devastating medical consequences, lung cancer (LC) and peripheral arterial disease (PAD)—solid arrow path on right side. We do not know at this time whether the structural link between the members of this nicotinic acetylcholine receptor (nAChR) subunit cluster (a) plays a role in the association; whether the polymorphism in this cluster can directly increase the sensitivity of the target tissues to tobacco smoke and/or nicotine toxicity—dashed arrow connecting (a and b); or whether all the increase in lung cancer and peripheral arterial disease can be indirectly ascribed to the behavioral effects of the α3/α5/β4 variant on smoking quantity and risk of nicotine addiction (c). (The approximate distributions of the α3 (red), α5 (blue) and β4 (gray) nAChR subunits are schematically depicted in the coronal section of a mouse brain shown on the right side of (b).)
| Name | Type |
|---|---|
| anxiety | phenotype |
| cancer | phenotype |
| Chrna3 | gene |
| CHRNA3 variant local | variant |
| CHRNA5 | gene |
| CHRNA5 variant local | variant |
| Chrnb4 | gene |
| CHRNB4 variant local | variant |
| cigarettes | phenotype |
| death | phenotype |
| deCODE | cohort |
| depression | phenotype |
| epilepsy | phenotype |
| genome-wide association studies | cohort |
| habenula | anatomy |
| Habenula-interpeduncular tract local | anatomy |
| Icelandic smokers local | cohort |
| lung cancer | phenotype |
| medical consequences | phenotype |
| mortality | phenotype |
| nAChR cluster variant local | variant |
| nicotine | drug |
| nicotine addiction | phenotype |
| nicotine dependence | phenotype |
| nicotine-induced behaviors local | phenotype |
| Nicotinic receptor antagonists local | drug |
| Nitrosamine-dependent malignant transformation local | phenotype |
| nonclassical pharmacotherapeutics local | drug |
| peripheral arterial disease | phenotype |
| preventable disease local | phenotype |
| psychoactive effects of nicotine local | phenotype |
| Reward phenomena local | phenotype |
| smoking | phenotype |
| smoking associated pathology local | phenotype |
| striatum | anatomy |
| substance use | phenotype |
| tobacco smoke | phenotype |
| tobacco use | phenotype |
| United States | cohort |
| withdrawal | phenotype |
| α3/α5/β4 subunit cluster local | drug |
| α3/α5/β4 variant local | variant |
No uploaded files.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| The genetics of substance dependence. | 2012 | 22703173 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence. | Lee SH et al. | — | 2018 | → |
| Re-defininG AddiC(CH3)Tion: genomics and epigenomics on substance use disorders. | Rutter JL et al. | — | 2014 | → |
| Functional characterization of SNPs in CHRNA3/B4 intergenic region associated with drug behaviors. | Flora AV et al. | — | 2013 | → |
| The CHRNA5-A3-B4 gene cluster in nicotine addiction. | Berrettini WH et al. | — | 2012 | → |
| The genetics of substance dependence. | Wang JC et al. | — | 2012 | → |
| Addiction as a systems failure: focus on adolescence and smoking. | Baler RD et al. | — | 2011 | → |
| Transcriptional and epigenetic mechanisms of addiction. | Robison AJ et al. | — | 2011 | → |
| A risky business--identifying susceptibility loci for lung cancer. | Gazdar AF et al. | — | 2010 | → |
| Smoking, nicotine and neuropsychiatric disorders. | Dome P et al. | — | 2010 | → |
| Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions. | Greenbaum L et al. | — | 2009 | → |