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The homozygous P582S mutation in the oxygen‐dependent degradation domain of HIF‐1α is associated with increased risk for prostate cancer
Author(s) -
OrrUrtreger Avi,
BarShira Anat,
Matzkin Haim,
Mabjeesh Nicola J.
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20433
Subject(s) - prostate cancer , prostate , medicine , mutation , hypoxia (environmental) , hif1a , cancer , pathological , cancer research , hypoxia inducible factor 1 , biology , oncology , endocrinology , gene , transcription factor , genetics , oxygen , chemistry , angiogenesis , organic chemistry
BACKGROUND The heterodimeric transcription factor HIF‐1 (hypoxia‐inducible factor 1), consisting of a critically regulated HIF‐1α subunit and a constitutively expressed HIF‐1β subunit, is a master regulator of genes involved in adaptation and survival under low‐oxygen conditions. Increased levels of HIF‐1 activity are associated with increased tumor aggressiveness, therapeutic resistance, and mortality. METHODS We studied 402 prostate cancer patients for the presence of the 1772C > T (P582S) and 1790G > A (A588T) mutations within the oxygen‐dependent domain of HIF‐1α. RESULTS Homozygosity for the P582S mutation was fourfold greater among prostate cancer patients compared to controls (OR = 4.10 [C.I. 95% 1.11 < OR < 17.87], P = 0.018). The existence of this mutation in prostate cancer patients was not associated with any of the clinical or pathological characteristics of the disease. No significant differences were found between the frequencies of A588T mutation in prostate cancer patients and controls. CONCLUSIONS Our data suggest that homozygous HIF1A P582S mutation confers significant susceptibility to prostate cancer. Prostate 67:8–13, 2007. © 2006 Wiley‐Liss, Inc.