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IGF‐I and IGFBP‐3 polymorphisms and risk of prostate cancer
Author(s) -
Friedrichsen Danielle M.,
Hawley Sarah,
Shu Jainfen,
Humphrey Mariela,
Sabacan Leah,
Iwasaki Lori,
Etzioni Ruth,
Ostrander Elaine A.,
Stanford Janet L.
Publication year - 2005
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.20259
Subject(s) - prostate cancer , medicine , odds ratio , endocrinology , prostate , allele , genotype , case control study , cancer , oncology , biology , genetics , gene
Abstract BACKGROUND Insulin‐like growth factor‐I (IGF‐I) is a potent mitogen for both normal and malignant prostate epithelial cells. The majority of circulating IGF‐I is bound in a complex with IGF binding protein‐3 (IGFBP‐3), which in turn limits IGF‐I bioavailability. Multiple studies suggest that higher IGF‐I and/or lower IGFBP‐3 serum levels are positively associated with prostate cancer risk. Several polymorphisms within the IGF‐I and IGFBP‐3 coding regions have been associated with increased serum protein levels. METHODS To ascertain the potential relationship between serum levels and polymorphism, and prostate cancer risk, we investigated the role of two polymorphisms the IGF‐I cytosine‐adenosine (CA)‐repeat and the IGFBP‐3 Ala32Gly, and prostate cancer in a population‐based, case‐control, study of middle‐aged men. RESULTS We found no significant association between the IGFBP‐3 Ala32Gly polymorphism and prostate cancer risk, even though the presence of at least one Gly allele did correlate with increased serum levels of IGFBP‐3. For IGF‐I , more controls (42%) than cases (38%) were homozygous for 19‐CA‐repeats (odds ratio, OR = 0.85; 95% confidence interval (CI) = 0.66–1.09). After stratifying by disease characteristics, 19‐CA‐repeat homozygous men displayed a decreased risk of low‐grade disease (OR = 0.50; 95% CI = 0.27–0.93), but no associations were observed with more aggressive features of disease. Additionally, there was no correlation between mean serum IGF‐I protein levels and IGF‐I genotype in controls. CONCLUSIONS Further evaluation of the IGF‐I CA‐repeat polymorphism and prostate cancer is necessary to determine if the modest risk reduction associated with the 19‐CA‐repeat homozygous state is observed in other study populations. © 2005 Wiley‐Liss, Inc.