This career development award will provide crucial training and experience in population genetics, bioinformatics, haplotyping, and tag SNP identification for Cathryn Bock, Ph.D. She is an Assistant Professor at Karmanos Cancer Institute and Wayne State University, proposing formal training and research under the mentorship of Ann Schwartz, Ph.D. and Rick Kittles, Ph.D., who have considerable expertise in these areas. In addition to attending relevant classes, seminars, and meetings, she will examine genes in the oxidative stress pathway, antioxidant intake and their potential interaction effects on racial disparities in prostate cancer incidence and progression in a sample of African American (AA) and European American men from metropolitan Detroit. Despite the considerable morbidity and mortality associated with prostate cancer, neither the etiology of the disease is not well characterized, nor are the large racial disparities. Oxidative stress has been proposed as one mechanism of prostate cancer initiation and progression, and early evidence supports this hypothesis. However, the specific role of genes in the oxidative stress pathway and their interactions with dietary and supplemental antioxidants are not yet well understood. Furthermore, it is possible that some of the racial differences in prostate cancer risk and progression may be explained by differences in genes involved in the oxidative stress pathway and their interaction with antioxidant intake. Therefore, this study will first estimate ancestry of the AA subjects using ancestry-informative markers from a previous study. Tag SNPs in three genes in the oxidative stress pathway, SOD2, OGG1, and GPX1 will then be identified. We will next assess whether variation in these genes modifies prostate cancer risk associated with intake of the antioxidants vitamin E, selenium and lycopene. Furthermore, each of these potential interactions will be examined by race and by prostate cancer aggressiveness to see if these oxidative stress pathway measures explain racial differences or disease progression. All analyses within the AA men will control for ancestry. DMA for analysis, interview, questionnaire, and medical record data will come from participants in an existing case-control study of prostate cancer in which enrollment recently was completed (PI: Benjamin A. Rybicki, Ph.D.). There are 275 AA men and 362 EA men with prostate cancer and 99 AA and 125 EA age- and race-matched men without prostate cancer enrolled in the case-control study with available data and blood samples and eligible for inclusion. This training is essential for Dr. Bock's transition to being an independent researcher in the genetic epidemiology of cancer. The identification of genetic markers for prostate cancer risk and progression, and of racial differences in the interaction of these markers with intake of antioxidants will improve screening techniques and prevention targeting efforts.
| Bock, Cathryn Hufford; Schwartz, Ann G; Ruterbusch, Julie J et al. (2009) Results from a prostate cancer admixture mapping study in African-American men. Hum Genet 126:637-42 |
