Prostate cancer incidence and mortality rates continue to be higher among African Americans than Caucasians. While psychosocial factors may explain some of the disparities, the role played by genetic differences in the two racial groups is not so clear. Emerging evidence suggests an important role of chronic or recurrent inflammation in prostate carcinogenesis. Interleukin-1 (IL-1) and IL-6 are inflammatory genes reported to be associated with prostate cancer risk. Interleukin-1 and IL-6 cytokines also decrease bone mineral density (BMD) by inducing osteoclasts to resorb bone matrix. We sought to determine if genotypes of IL-1A, IL-1B, IL-1RN, IL-6 and IL-6R were associated with prostate cancer risk, as well as with selected risk factors, in the two racial groups.
We examined allele frequency distributions of polymorphisms in IL-1A, IL-1B, IL-1RN, IL-6 and IL-6R genes in a cross-sectional study of African American and Caucasian men ages 40 to 80 years old. We also assessed the associations of genotypes of these inflammatory genes and the risk of prostate cancer in a case-control study of the two racial groups. Additionally, we evaluated the associations of bone mineral density and prostate cancer in our sample. We found racial differences in minor allele frequencies, as well as in the associations of single nucleotide polymorphisms of inflammatory genes IL-1 and IL-6 and prostate cancer. We also found associations of IL-1 and IL-6 genotypes and prostate cancer. Additionally, we found an inverse association of BMD and prostate cancer in both racial groups. Our findings support a growing body of evidence that chronic or recurrent inflammation play an important role in prostate carcinogenesis, and the possibility of ethnic based differences in susceptibility. Understanding the role of IL-1 and IL-6 genes in the development of prostate cancer is of great public health significance because it will enable their possible use as biomarkers for early detection and prompt intervention, increase our understanding of the molecular biology of the disease, open up new avenues for prevention and treatment, as well as explain some of the observed disparities in the disease.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04072009-200629 |
| Date | 29 June 2009 |
| Creators | Appenteng, Kwame Afari |
| Contributors | Joel Weissfeld, Robert Ferrell, John Wilson, Clareann Bunker |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04072009-200629/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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