Presentation Abstract

Abstract Number: 4724
Presentation Title: A novel region on 8q24.21 is associated with ovarian cancer susceptibility
Presentation Time: Tuesday, Apr 20, 2010, 2:00 PM - 5:00 PM
Location: Exhibit Hall A-C, Poster Section 34
Poster Section: 34
Poster Board Number: 8
Author Block: Ya-Yu Tsai1, Y. Ann Chen1, Zhihua Chen1, Jenny Permuth-Wey1, Edwin Iversen2, Harvey Risch3, Jill Barnholtz-Sloan4, Julie M. Cunningham5, Robert A. Vierkant5, Brooke L. Fridley5, David Fenstermacher1, Rebecca Sutphen1, Catherine M. Phelan1, Steve A. Narod6, Joellen M. Schildkraut2, Ellen L. Goode5, Thomas A. Sellers1. 1Moffitt Cancer Center and Research Institute, Tampa, FL; 2Duke University School of Medicine, Durham, NC; 3Yale University, New Haven, CT; 4Case Comprehensive Cancer Center, Case School of Medicine, Cleveland, OH; 5Mayo Clinic College of Medicine, Rochester, MN; 6Center for Research in Women's Health, Toronto, ON, Canada
Abstract Body: 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.