Abstract
Aims: Epidemiological evidence shows that diabetes is associated with a reduced risk of prostate cancer. The objective of this study was to identify genes that may contribute to both type 2 diabetes and prostate cancer outcomes and the biological pathways these diseases may share. Methods: The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities that included a baseline examination in 1987-89 and three follow-up exams at three year intervals. Participants were 45-64 years old at baseline. We conducted a genomewide association (GWA) study of incident type 2 diabetes in males, summarized variation across genetic loci into a polygenic risk score, and determined if that diabetes risk score was also associated with incident prostate cancer in the same study population. Secondarily we conducted a separate GWA study of prostate cancer, performed a pathway analysis of both type 2 diabetes and prostate cancer, and qualitatively determined if any of the biochemical pathways identified were shared between the two outcomes. Results: We found that the polygenic risk score for type 2 diabetes was not statistically significantly associated with prostate cancer. The pathway analysis also found no overlap between pathways associated with type 2 diabetes and prostate cancer. However, it did find that the growth hormone signaling pathway was statistically significantly associated with type 2 diabetes (p=0.0001). Conclusion: The inability of this study to find an association between type 2 diabetes polygenic risk scores with prostate cancer or biological pathways in common suggests that shared genetic variants may not contribute significantly to explaining shared etiology.
Original language | English (US) |
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Pages (from-to) | 49-60 |
Number of pages | 12 |
Journal | International Journal of Molecular Epidemiology and Genetics |
Volume | 4 |
Issue number | 1 |
State | Published - 2013 |
Keywords
- Pathway analysis
- Polygenic risk score
- Prostate cancer
- Type 2 diabetes