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Genetic and plasma variation of insulin‐like growth factor binding proteins in relation to prostate cancer incidence and survival
Author(s) -
Johansson Mattias,
McKay James D.,
Rinaldi Sabina,
Wiklund Fredrik,
Adami HansOlov,
Grönberg Henrik,
Kaaks Rudolf,
Stattin Pär
Publication year - 2009
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.20972
Subject(s) - igfbp3 , prostate cancer , single nucleotide polymorphism , lncap , medicine , oncology , endocrinology , prostate , genome wide association study , biology , cancer , growth factor , genotype , genetics , gene , receptor
BACKGROUND Binding proteins regulate bioavailability of insulin‐like growth factor‐I (IGF‐I) in the circulation and affect apoptosis of tumor cells in the prostate. We analyzed genetic variation within genes coding for IGF binding proteins in relation to prostate cancer incidence and survival. We also investigated if circulating IGFBP3 affects prostate cancer‐specific survival. MATERIALS AND METHODS Eleven haplotype tagging SNPs and two single SNPs in the IGFBP1 , IGFBP3 , and IGFALS genes were genotyped within the CAncer Prostate in Sweden (CAPS) study including 2,774 cases and 1,736 controls. Plasma samples for analyses of total‐ and intact IGFBP3 levels were available for 1,521 cases and 909 controls. Complete follow‐up of vital status was achieved by linkage to the Swedish Cause of Death Register. RESULTS We found no clear association between the genetic variants and prostate cancer incidence or survival. The rare allele of the IGFBP3 SNP rs2854744 was associated with elevated plasma levels of total IGFBP3 ( P trend = 9 × 10 −8 ), but not intact IGFBP3 ( P trend = 0.16). Elevated levels of total‐ ( P trend = 0.03) and intact IGFBP3 ( P trend = 6 × 10 −14 ) were associated with increased risk of prostate cancer specific death. Treatment and tumor characteristics accounted for the association with total IGFBP3, whereas the association with intact IGFBP3 was attenuated, but still statistically significant in adjusted analysis ( P trend‐adjusted = 0.0004). Elevated intact IGFBP3 was also significantly associated with increased risk of prostate cancer‐specific death among patients who were chemically or surgically castrated ( P trend‐adjusted = 0.0003), and among patients who had not been treated ( P trend‐adjusted = 0.02). CONCLUSIONS Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer‐specific death. Prostate 69:1281–1291, 2009. © 2009 Wiley‐Liss, Inc.