Effect of HIF-12 Alpha Polymorphism on the Incidence and Severity of Prostate
Annual rept. 7 Jan 2005-6 Jan 2006
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
Pagination or Media Count:
Hypoxia-inducible factor-1 HIF-1 plays an important role in tumor progression and metastasis and is overexpressed prostate cancer CaP. Two polymorphisms P582S C-T and A588T G-A in the HIF-1 gene have been associated with enhanced stability of the protein and may confer susceptibility to androgen independent CaP. We examined the association of these two HIF-1 gene polymorphisms with CaP risk among 1,072 incident cases diagnosed during 18 years of follow-up and 1,322 age matched controls in the Physicians Health Study We observed no association between the presence of these two polymorphisms and risk of total CaP. However, the HIF-1 P582S T variant allele carrier CT or TT vs. CC was associated with a nonsignificant increased risk of high-grade tumor Gleason 7-10 OR, 95 CI 1.31, 0.97-1.75Among the T allele carriers, but not the CC wildtype carriers, men with higher IGF-I levels median vs. median had increased risk for total OR, 95 CI 1.55, 0.96-2.48, aggressive stage C, D, Gleason 7-10, or fatal disease, OR, 95 CI 2.15, 1.04-4.43, and fatal CaP OR, 95 CI 4.91, 1.27-18.9. Higher IGFBP-3 levels median vs. median were associated with lower risk mainly among men with the homozygous CC genotype.
- Medicine and Medical Research