Effect of HIF-12 Alpha Polymorphism on the Incidence and Severity of Prostate
Abstract
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 Physician's 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA453331
Entities
People
- Glenn J. Bubley
Organizations
- Beth Israel Deaconess Medical Center