|Grant Number:||5R01CA058684-13 Interpret this number|
|Primary Investigator:||Stampfer, Meir|
|Organization:||Brigham And Women'S Hosp., Inc.|
|Project Title:||Hormones and Cytokines in Cap Risk and Recurrence|
DESCRIPTION (provided by applicant): Over the past decade, the NCI supported Physicians' Health Study (PHS) of biomarkers and prostate cancer has prospectively evaluated and demonstrated the importance of several risk factors or markers including prostate specific antigen, sex hormone levels, the androgen receptor polymorphism, and insulin-like growth factor-I and its binding protein-3. The importance of sex hormones in prostate cancer is well established, but several critical issues remain to be addressed. These include the impact of short- vs. long-term exposure, the validity of a single vs. multiple measurements, identification of genetic and lifestyle influences on hormone levels, effects of changes in hormone levels, and the association of hormones with specific clinical and pathological characteristics. In this competing renewal grant, we propose to address these specific issues using long-term archived blood samples collected at baseline (1982-1984) in the PHS I and a second blood sample collected from over 60% of the original participants during 1995-1998 in the PHS II (an ongoing randomized trial of nutritional supplements). We will also assess the role of several newly identified polymorphisms in the sex hormone metabolism pathways, receptors, and a prostate cancer susceptibility gene. Recent data suggest that transforming growth factor (TGF)-Beta1 and interleukin (IL)-6 play important roles in prostate tumorigenesis, angiogenesis. and progression. We propose to prospectively assess the role of prediagnostic levels of these factors and several of their genetic polymorphisms. We will further explore the clinical significance of circulating levels (and genetic variations) of hormones, TGF-Beta1 and IL-6 in relation to their expression in tumor tissue, angiogenesis and prostate cancer progression. In the PHS 1, we have already assembled an extensive prospective clinical and serological database on prostate cancer with almost two decades of follow-up of 14,916 men. The PHS II collected and archived 7.241 blood samples. The two blood samples collected between the PHS I and the PHS It among the same 9.436 participants provides a unique and cost-effective opportunity to study the hypotheses proposed here. The large number of cases (n=1 ,765) will provide sufficient statistical power to provide firm answers to these questions.
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.
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.
Vitamin and mineral supplements for cancer prevention: issues and evidence.
Authors: Fairfield K, Stampfer M
Source: Am J Clin Nutr, 2007 Jan;85(1), p. 289S-292S.
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.
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.
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.
Prostate-specific antigen and free prostate-specific antigen in the early detection of prostate cancer: do combination tests improve detection?
Authors: Etzioni R, Falcon S, Gann PH, Kooperberg CL, Penson DF, Stampfer MJ
Source: Cancer Epidemiol Biomarkers Prev, 2004 Oct;13(10), p. 1640-5.
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 selenium levels and prostate cancer risk.
Authors: Li H, Stampfer MJ, Giovannucci EL, Morris JS, Willett WC, Gaziano JM, Ma J
Source: J Natl Cancer Inst, 2004 May 5;96(9), p. 696-703.
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.
Combining biomarkers to detect disease with application to prostate cancer.
Authors: Etzioni R, Kooperberg C, Pepe M, Smith R, Gann PH
Source: Biostatistics, 2003 Oct;4(4), p. 523-38.
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.
Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer.
Authors: Chan JM, Stampfer MJ, Ma J, Gann P, Gaziano JM, Pollak M, Giovannucci E
Source: J Natl Cancer Inst, 2002 Jul 17;94(14), p. 1099-106.
Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function.
Authors: Gelmann EP, Steadman DJ, Ma J, Ahronovitz N, Voeller HJ, Swope S, Abbaszadegan M, Brown KM, Strand K, Hayes RB, Stampfer MJ
Source: Cancer Res, 2002 May 1;62(9), p. 2654-9.
Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study.
Authors: Chan JM, Stampfer MJ, Ma J, Gann PH, Gaziano JM, Giovannucci EL
Source: Am J Clin Nutr, 2001 Oct;74(4), p. 549-54.
Approximating the distribution of maximally selected McNemar's statistics.
Authors: Rabinowitz D, Betensky RA
Source: Biometrics, 2000 Sep;56(3), p. 897-902.
The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer.
Authors: Febbo PG, Kantoff PW, Platz EA, Casey D, Batter S, Giovannucci E, Hennekens CH, Stampfer MJ
Source: Cancer Res, 1999 Dec 1;59(23), p. 5878-81.
Debrisoquine hydroxylase (CYP2D6) and prostate cancer.
Authors: Febbo PG, Kantoff PW, Giovannucci E, Brown M, Chang G, Hennekens CH, Stampfer M
Source: Cancer Epidemiol Biomarkers Prev, 1998 Dec;7(12), p. 1075-8.