Abstract 868: Replication of melanoma GWAS hits and exploration of pleiotropic effects of cancer GWAS hits with melanoma risk in the PAGE study

Abstract

Introduction: As the most serious form of skin cancer, melanoma is a considerable public health burden. Genome wide association studies (GWAS) have successfully identified several loci important to melanoma susceptibility. Some of these loci have been associated with other cancers as well, similar to the pleiotropy previously demonstrated in the 8q24 and TERT regions. Such pleiotropy can highlight important regions and may help inform variant functionality. However, the potential pleiotropic effects of gene variants identified for other cancers have not been fully explored for melanoma. This study evaluates whether GWAS hits for melanoma, as well as hits for non-melanoma cancers, are associated with melanoma risk.Methods: We included 918 white melanoma cases and 4495 white controls in the Women's Health Initiative, which were genotyped as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. We evaluated 8 single nucleotide polymorphisms (SNPs) previously shown to be associated with melanoma in GWAS as well as 175 SNPs previously shown to be associated with other cancers. These findings were mostly based on GWAS in Caucasian populations. We used logistic regression to evaluate the association between each SNP and melanoma risk, using an age-adjusted additive genetic model.Results: Of the 8 melanoma SNPs evaluated, 7 were statistically significantly associated with melanoma risk (p<0.05). These SNPs were rs1393350 (p=0.001), rs16891982 (p=3.34e-05), rs258322 (p=1.53e-9), rs4785763 (p=3.29e-4), rs7023329 (p=2.20e-5), rs910873 (p=2.38e-4), and rs4636294 (p=5.82e-5). For each of these significant SNPs, the association was in the same direction of risk as previously reported. The SNP that did not replicate was rs2284063 (p=0.38). Our analysis for pleotropic effects of other cancer GWAS hits did not yield any significant associations after adjustment for multiple comparisons (p=2.87e-4). The most significant SNP was rs710521 (p=0.006), previously associated with urinary bladder cancer.Conclusions: This preliminary analysis demonstrates that nearly all previously discovered melanoma SNPs replicated. Our analysis did not discover any non-melanoma cancer SNPs that are also associated with melanoma. The next step in this analysis will be to incorporate data from the other three PAGE studies: the Multiethnic Cohort (MEC), Epidemiologic Architecture of Genes Linked to Environment (EAGLE), and the CALiCo Consortium (see pagestudy.org). This will substantially improve the power of our pleiotropy analyses.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 868. doi:10.1158/1538-7445.AM2011-868