Despite widespread screening and improved treatment, prostate cancer (CaP) remains a major public health concern with more than 192,290 cases diagnosed in the US annually. Significant racial disparities exist, with African Americans (AA) facing a 70% higher incidence of CaP compared to Caucasian/European Americans (EA), higher than any other ethnic group in the US. Quantitative estimates from twin studies indicate that 42% of the variation in CaP risk may be attributed to genetic componentshigher than for any other type of common human cancer. Genome-wide association studies (GWAS) have identified a number of common SNPs that are associated with CaP risk in populations of European descent, although these SNPs explain only a small fraction of the heritable component. Replication and fine mapping studies of these SNPs have focused largely on Europeans. AAs have been evaluated less frequently despite their higher risk of CaP. We established a panel of 800 SNPs including 32 SNPs from European-based GWAS and 35 flanking SNPs. Using these SNPs we genotyped blood samples from 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared them to 925 AA and 1,687 EA controls from Illuminas iControlDB. Of the 32 GWAS SNPs, 13 were significant at P <0.05 in EA and 4 in AA. Three of 35 flanking SNPs, all from chromosome 8q, reached study-wide significance (p <3.510-5);two in AA and one in EA. Among the remaining 656 SNPs, two were associated with CaP (p <3.510-5) and both were located in intergenic regions. For the 32 GWAS SNPs, we used receiver operator curve plots to examine whether these SNPs could be used to classify men at high risk of developing prostate cancer. We obtained area under the curve (AUC) estimates of 0.60 and 0.56 for EA and AA respectively. This study confirms a large proportion of CaP associated regions implicated by European-based GWAS and provides evidence that some regions may be important in AA CaP risk. But despite the identification of a large panel of GWAS replicated SNPs for CaP, AUC estimates demonstrate that this panel is not appropriate for clinical screening. We are now extending this work to a larger number of men with additional SNPs in order to investigate whether SNPs are associated with prostate cancer aggressiveness. A manuscript is in preparation.
| O'Brien, Katie M; Sandler, Dale P; Xu, Zongli et al. (2018) Vitamin D, DNA methylation, and breast cancer. Breast Cancer Res 20:70 |
| Herceg, Zdenko; Ghantous, Akram; Wild, Christopher P et al. (2018) Roadmap for investigating epigenome deregulation and environmental origins of cancer. Int J Cancer 142:874-882 |
| Wu, Lang; Shi, Wei; Long, Jirong et al. (2018) A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet 50:968-978 |
| O'Brien, Katie M; Sandler, Dale P; Shi, Min et al. (2018) Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women. Front Genet 9:67 |
| O'Brien, Katie M; Sandler, Dale P; Kinyamu, H Karimi et al. (2017) Single-Nucleotide Polymorphisms in Vitamin D-Related Genes May Modify Vitamin D-Breast Cancer Associations. Cancer Epidemiol Biomarkers Prev 26:1761-1771 |
| Wilson, L E; Harlid, S; Xu, Z et al. (2017) An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort. Int J Obes (Lond) 41:194-199 |
| Michailidou, Kyriaki (see original citation for additional authors) (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 551:92-94 |
| Sandler, Dale P; Hodgson, M Elizabeth; Deming-Halverson, Sandra L et al. (2017) The Sister Study Cohort: Baseline Methods and Participant Characteristics. Environ Health Perspect 125:127003 |
| Amos, Christopher I; Dennis, Joe; Wang, Zhaoming et al. (2017) The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers. Cancer Epidemiol Biomarkers Prev 26:126-135 |
| Milne, Roger L (see original citation for additional authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49:1767-1778 |
Showing the most recent 10 out of 50 publications
