Abstract 49: The association of genetic variants in dopamine regulators with indoor tanning and melanoma.

Ultraviolet radiation (UVR) is the main etiologic factor associated with the development of melanoma and there is now strong evidence to support an increased risk of melanoma incidence with exposure to UVR emitting indoor tanning devices. Most frequent tanners have an appropriate knowledge of the health risks associated with indoor tanning but continue to tan despite these risks. A relatively large percentage of frequent indoor tanners display addictive behavior implicating the involvement of complex factors in the persistent desire to tan indoors. Genetic factors are thought to play a role in biological reward pathways that reinforce addictive behavior such as with alcohol or nicotine dependency. In addition, UVR is hypothesized to modify biological pathways, for example through the dopamine neurotransmitter system, to reinforce tanning behavior. No studies to date have examined variants in genes involved with dopamine regulation and drug metabolism with indoor tanning behavior and risk for melanoma. We examined the association of 68 single nucleotide polymorphisms (SNPs) in 5 dopamine receptor and drug metabolism genes in DNA from participants of the Skin Health Study, a study in Minnesota developed to assess the risk of melanoma with indoor tanning behavior. The Skin Health Study recruited individuals with cutaneous melanoma (cases) and without melanoma (controls) between the ages of 25-59 in Minnesota from 2004 to 2007. Detailed information on lifetime indoor tanning behavior was collected by interview that was partially self-administered and partially telephone-administered. DNA samples were obtained from mouthwash, and DNA was genotyped using the Illumina GoldenGate platform. The association of SNPs with melanoma was assessed by logistic regression in cases (n=894) and controls (n=799). Due to possible confounding of tanning behavior and melanoma, the association of SNPs with having ever or never tanned indoors was assessed in controls only. Participants with variants in the DRD2 dopamine receptor gene and the ANKK1 signaling gene were more likely to have ever tanned indoors compared to those without DRD2 and ANKK1 variants. Variants in DRD2 and ANKK1 were also associated with increased risks for melanoma (rs1003641 OR=1.18, CI: 1.01, 1.38; rs2734831 OR=1.17, CI 1.01, 1.35). The interactions of one ANKK1 SNP and 3 DRD2 SNPs with tanning behavior were significantly associated with risk for melanoma (p < 0.05 for all). These data suggest that variants in dopamine receptors could mediate tanning behavior that ultimately influences risk for melanoma. The DRD2 and ANKK1 alleles represent important genomic regions for further investigations to explore addictive tanning behavior. Citation Format: Kristina G. Flores, Esther Erdei, Li Luo, Kirsten A.M. White, Marianne Berwick, DeAnn Lazovich. The association of genetic variants in dopamine regulators with indoor tanning and melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 49.