Abstract 4724: A novel region on 8q24.21 is associated with ovarian cancer susceptibility
Authors: Tsai Ya-Yu , Chen Y. Ann , Chen Zhihua , Permuth-Wey Jenny , Iversen Edwin , Risch Harvey , Barnholtz-Sloan Jill , Cunningham Julie M. , Vierkant Robert A. , Fridley Brooke L. , Fenstermacher David , Sutphen Rebecca , Phelan Catherine M. , Narod Steve A. , Schildkraut Joellen M. , Goode Ellen L. , Sellers Thomas A. 
Published: February 2011

Abstract
Recent GWAS have identified and confirmed associations between several SNPs in the gene desert located on chromosome 8q24 with risk of cancers of the breast, prostate, glioma, bladder and colorectum. Evidence supporting an association with ovarian cancer is limited and inconsistent.
Here we evaluate preliminary results in the 8q24 region from stage I of an ongoing invasive epithelial ovarian cancer GWAS among 1864 cases (1096 serous cases) and 1912 controls. All subjects were self-reported non-Hispanic non-Jewish Caucasian, and were genotyped with the Illumina 610quad Chip. Samples and SNPs with call rates less than 95% were excluded (9.6% and 9.9%, respectively) as well as 128 subjects with ambiguous gender, unresolved identical genotypes and less than 80% European ancestry were also excluded. Our most significant hit in the region was rs6651252 located at 8q24.21 with p = 0.000125 for all ovarian cancer, and 1.02*10−5 for serous cases only. This region is located approximately 849 kb downstream of the previous 8q24.21 findings on other cancers, and was not in linkage disequilibrium with any of the haplotype blocks reported previously. We further examined the block structure of this region with eight genotyped SNPs located within 129.61 to 129.64 MB (rs10088218, rs1516973, rs1516975, rs16903097, rs10098821, rs6651252, rs1561928, and rs1561927) and performed haplotype analysis to evaluate the association with ovarian cancer risk. One haplotype (AAGCAGGG, estimated frequency=0.11) was significantly associated with decreased ovarian cancer risk with an odds ratio of 0.67 (all cases, 95% CI: 0.78-0.91, p=0.0026, empirical p= 0.0020). This region contains no known genes, but it is located upstream and overlaps with a known copy number variation (CNV) reported by Redon et al. (2006). Previous published literature on array CGH and CNV results from TCGA (The Cancer Genome Atlas) also indicate that the 8q24.21 region is associated with frequent gains/amplification in ovarian tumors. Combined analysis of SNPs and CNV identified in this region is underway to elucidate the joint effect of these two types of genetic variation on ovarian cancer risk. Our result indicates a novel locus on 8q24.21 is associated with epithelial ovarian cancer susceptibility. Haplotype analysis reveals one specific haplotype that is associated with decreased ovarian cancer risk compared to the most common haplotype. Given previous 8q24 findings from other cancers and evidence from publicly available resources, fine-mapping and resequencing of this region is warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4724.