|Grant Number:||3R01CA090598-05S1 Interpret this number|
|Primary Investigator:||Stampfer, Meir|
|Organization:||Brigham And Women'S Hosp., Inc.|
|Project Title:||Growth Factors and Prostate Cancer Risk|
Widespread prostate specific antigen (PSA) screening underscores the need to identify causes and potential biomarkers of clinically more aggressive prostate cancer. Laboratory and clinical studies suggest that growth factors play an important role in prostate cancer proliferation, apoptosis and angiogenesis. These growth factors include insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF). In the Physicians Health Study (PHS), we recently showed that prediagnostic levels of circulating IGF-I were significantly associated with prostate cancer risk, while high levels of IGF binding protein, IGFBP-3, were associated with lower risk. Furthermore, our pilot study data suggests that plasma VEGF levels are significantly higher among patients with metastatic disease compared to patients with localized prostate cancer, and that plasma VEGF levels in advanced prostate cancer patients are prognostic for survival. To understand the underlying nature of these associations, we now propose to extend our previous work on IGF-I and IGFBP-3 to examine the associations of free IGF-I, IGFBP-I, a newly identified polymorphism of IGFBP-3, and circulating levels of VEGF in relation to risk of total and aggressive prostate cancer. We plan to obtain prostate cancer tissue samples from 828 cases to establish biologic links between these epidemiologic findings and phenotypic features of prostate cancer. We will assess the associations of these growth factors with tissue markers for disease progression, including IGF-I downstream signaling (HIF-1 and PTEN), markers of cellular proliferation rate (Ki67), apoptosis (TUNEL), and angiogenesis (VEGF expression and microvascular density). We will also examine the relation of these plasma and tissue markers with prostate cancer relapse and mortality. In the PHS, we have already assembled an extensive prospective clinical and serological database on prostate cancer with almost two decades of follow-up and 1336 prostate cancers. With this proposed study, we will expand upon our epidemiological findings and examine the biology underlying these intriguing results.
Blood levels of saturated and monounsaturated fatty acids as markers of de novo lipogenesis and risk of prostate cancer.
Authors: Chavarro JE, Kenfield SA, Stampfer MJ, Loda M, Campos H, Sesso HD, Ma J
Source: Am J Epidemiol, 2013 Oct 15;178(8), p. 1246-55.
EPub date: 2013 Aug 28.
Circulating levels of vitamin D and colon and rectal cancer: the Physicians' Health Study and a meta-analysis of prospective studies.
Authors: Lee JE, Li H, Chan AT, Hollis BW, Lee IM, Stampfer MJ, Wu K, Giovannucci E, Ma J
Source: Cancer Prev Res (Phila), 2011 May;4(5), p. 735-43.
EPub date: 2011 Mar 23.
A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival.
Authors: Li H, Stampfer MJ, Mucci L, Rifai N, Qiu W, Kurth T, Ma J
Source: Clin Chem, 2010 Jan;56(1), p. 34-43.
EPub date: 2009 Nov 12.
Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer.
Authors: Schernhammer ES, Giovannucci E, Kawasaki T, Rosner B, Fuchs CS, Ogino S
Source: Gut, 2010 Jun;59(6), p. 794-9.
EPub date: 2009 Oct 14.
A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status.
Authors: Schernhammer ES, Giovannuccci E, Fuchs CS, Ogino S
Source: Cancer Epidemiol Biomarkers Prev, 2008 Oct;17(10), p. 2895-8.
Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis.
Authors: Ma J, Li H, Giovannucci E, Mucci L, Qiu W, Nguyen PL, Gaziano JM, Pollak M, Stampfer MJ
Source: Lancet Oncol, 2008 Nov;9(11), p. 1039-47.
EPub date: 2008 Oct 3.
Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression.
Authors: Schernhammer ES, Ogino S, Fuchs CS
Source: Gastroenterology, 2008 Sep;135(3), p. 770-80.
EPub date: 2008 Jun 12.
Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women.
Authors: Michaud DS, Wolpin B, Giovannucci E, Liu S, Cochrane B, Manson JE, Pollak MN, Ma J, Fuchs CS
Source: Cancer Epidemiol Biomarkers Prev, 2007 Oct;16(10), p. 2101-9.
EPub date: 2007 Sep 28.
A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk.
Authors: Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J
Source: Cancer Epidemiol Biomarkers Prev, 2007 Jul;16(7), p. 1364-70.
EPub date: 2007 Jun 21.
Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts.
Authors: Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C
Source: Cancer Res, 2007 Jun 1;67(11), p. 5553-60.
C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women.
Authors: Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E
Source: Cancer Epidemiol Biomarkers Prev, 2006 Apr;15(4), p. 750-5.
Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma.
Authors: Schernhammer ES, Tranah GJ, Giovannucci E, Chan AT, Ma J, Colditz GA, Hunter DJ, Willett WC, Fuchs CS
Source: Br J Cancer, 2006 Mar 27;94(6), p. 928-34.
Prediagnostic plasma vascular endothelial growth factor levels and risk of prostate cancer.
Authors: Li H, Kantoff PW, Ma J, Stampfer MJ, George DJ
Source: Cancer Epidemiol Biomarkers Prev, 2005 Jun;14(6), p. 1557-61.
Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study.
Authors: Tranah GJ, Chan AT, Giovannucci E, Ma J, Fuchs C, Hunter DJ
Source: Mol Carcinog, 2005 Sep;44(1), p. 21-30.
Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women.
Authors: Wei EK, Giovannucci E, Selhub J, Fuchs CS, Hankinson SE, Ma J
Source: J Natl Cancer Inst, 2005 May 4;97(9), p. 684-92.
APC Asp1822Val and Gly2502Ser polymorphisms and risk of colorectal cancer and adenoma.
Authors: Tranah GJ, Giovannucci E, Ma J, Fuchs C, Hunter DJ
Source: Cancer Epidemiol Biomarkers Prev, 2005 Apr;14(4), p. 863-70.
A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women.
Authors: Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E
Source: Cancer Epidemiol Biomarkers Prev, 2005 Apr;14(4), p. 850-5.
Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer.
Authors: Li H, Kantoff PW, Giovannucci E, Leitzmann MF, Gaziano JM, Stampfer MJ, Ma J
Source: Cancer Res, 2005 Mar 15;65(6), p. 2498-504.
Prospective study of plasma carotenoids and tocopherols in relation to risk of ischemic stroke.
Authors: Hak AE, Ma J, Powell CB, Campos H, Gaziano JM, Willett WC, Stampfer MJ
Source: Stroke, 2004 Jul;35(7), p. 1584-8.
EPub date: 2004 Jun 3.
A gain of function TGFB1 polymorphism may be associated with late stage prostate cancer.
Authors: Ewart-Toland A, Chan JM, Yuan J, Balmain A, Ma J
Source: Cancer Epidemiol Biomarkers Prev, 2004 May;13(5), p. 759-64.
A prospective study of plasma C-peptide and colorectal cancer risk in men.
Authors: Ma J, Giovannucci E, Pollak M, Leavitt A, Tao Y, Gaziano JM, Stampfer MJ
Source: J Natl Cancer Inst, 2004 Apr 7;96(7), p. 546-53.
The role of metastasis-associated protein 1 in prostate cancer progression.
Authors: Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, Gschwend JE, Hautmann RE, Sanda MG, Giehl K, Menke A, Chinnaiyan AM, Rubin MA
Source: Cancer Res, 2004 Feb 1;64(3), p. 825-9.
Plasma carotenoids and tocopherols and risk of myocardial infarction in a low-risk population of US male physicians.
Authors: Hak AE, Stampfer MJ, Campos H, Sesso HD, Gaziano JM, Willett W, Ma J
Source: Circulation, 2003 Aug 19;108(7), p. 802-7.
EPub date: 2003 Aug 4.