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 x 10(-8)), but not intact IGFBP3 (P(trend) = 0.16). Elevated levels of total- (P(trend) = 0.03) and intact IGFBP3 (P(trend) = 6 x 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.
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 x 10(-8)), but not intact IGFBP3 (P(trend) = 0.16). Elevated levels of total- (P(trend) = 0.03) and intact IGFBP3 (P(trend) = 6 x 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.
Authors: Konstantinos K Tsilidis; Ruth C Travis; Paul N Appleby; Naomi E Allen; Sara Lindström; Demetrius Albanes; Regina G Ziegler; Marjorie L McCullough; Afshan Siddiq; Aurelio Barricarte; Sonja I Berndt; H Bas Bueno-de-Mesquita; Stephen J Chanock; E David Crawford; W Ryan Diver; Susan M Gapstur; Edward Giovannucci; Fangyi Gu; Christopher A Haiman; Richard B Hayes; David J Hunter; Mattias Johansson; Rudolf Kaaks; Laurence N Kolonel; Peter Kraft; Loic Le Marchand; Kim Overvad; Silvia Polidoro; Elio Riboli; Fredrick R Schumacher; Victoria L Stevens; Dimitrios Trichopoulos; Jarmo Virtamo; Walter C Willett; Timothy J Key Journal: Int J Cancer Date: 2013-02-15 Impact factor: 7.396
Authors: Yin Cao; Sara Lindström; Fredrick Schumacher; Victoria L Stevens; Demetrius Albanes; Sonja Berndt; Heiner Boeing; H Bas Bueno-de-Mesquita; Federico Canzian; Saioa Chamosa; Stephen J Chanock; W Ryan Diver; Susan M Gapstur; J Michael Gaziano; Edward L Giovannucci; Christopher A Haiman; Brian Henderson; Mattias Johansson; Loïc Le Marchand; Domenico Palli; Bernard Rosner; Afshan Siddiq; Meir Stampfer; Daniel O Stram; Rulla Tamimi; Ruth C Travis; Dimitrios Trichopoulos; Walter C Willett; Meredith Yeager; Peter Kraft; Ann W Hsing; Michael Pollak; Xihong Lin; Jing Ma Journal: J Natl Cancer Inst Date: 2014-06 Impact factor: 13.506
Authors: Sean Harrison; Rosie Lennon; Jeff Holly; Julian P T Higgins; Mike Gardner; Claire Perks; Tom Gaunt; Vanessa Tan; Cath Borwick; Pauline Emmet; Mona Jeffreys; Kate Northstone; Sabina Rinaldi; Stephen Thomas; Suzanne D Turner; Anna Pease; Vicky Vilenchick; Richard M Martin; Sarah J Lewis Journal: Cancer Causes Control Date: 2017-03-30 Impact factor: 2.506
Authors: Carolina Bonilla; Sarah J Lewis; Mari-Anne Rowlands; Tom R Gaunt; George Davey Smith; David Gunnell; Tom Palmer; Jenny L Donovan; Freddie C Hamdy; David E Neal; Rosalind Eeles; Doug Easton; Zsofia Kote-Jarai; Ali Amin Al Olama; Sara Benlloch; Kenneth Muir; Graham G Giles; Fredrik Wiklund; Henrik Grönberg; Christopher A Haiman; Johanna Schleutker; Børge G Nordestgaard; Ruth C Travis; Nora Pashayan; Kay-Tee Khaw; Janet L Stanford; William J Blot; Stephen Thibodeau; Christiane Maier; Adam S Kibel; Cezary Cybulski; Lisa Cannon-Albright; Hermann Brenner; Jong Park; Radka Kaneva; Jyotsna Batra; Manuel R Teixeira; Hardev Pandha; Mark Lathrop; Richard M Martin; Jeff M P Holly Journal: Int J Cancer Date: 2016-06-23 Impact factor: 7.396