Blood Levels of Saturated and Monounsaturated Fatty Acids as Markers of De Novo Lipogenesis and Risk of Prostate Cancer

被引:60
作者
Chavarro, Jorge E. [1 ,2 ,3 ]
Kenfield, Stacey A. [4 ]
Stampfer, Meir J. [1 ,2 ,3 ]
Loda, Massimo [5 ,6 ]
Campos, Hannia [1 ]
Sesso, Howard D. [7 ]
Ma, Jing [3 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02115 USA
[4] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA
[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Ctr Mol Oncol Pathol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
biomarkers; epidemiology; fatty acids; nutrition; prostate cancer; BODY-MASS INDEX; ADIPOSE-TISSUE; WHOLE-BLOOD; SYNTHASE; PLASMA; INHIBITION; EXPRESSION; APOPTOSIS; GROWTH; OVEREXPRESSION;
D O I
10.1093/aje/kwt136
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
De novo lipogenesis has been implicated in prostate carcinogenesis, and blood levels of specific saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) could reflect activity of this pathway. We used gas chromatography to measure blood SFA and MUFA levels in prediagnostic samples from 476 incident prostate cancer cases (19821995) in the Physicians Health Study and an equal number of controls matched on age and smoking status. Five tagging polymorphisms in the fatty acid synthase (FASN) gene (rs1127678, rs6502051, rs4246444, rs12949488, and rs8066956) were related to blood SFA and MUFA levels. Conditional logistic regression was used to estimate the rate ratios, with 95 confidence intervals, of prostate cancer across quintiles of blood fatty acid levels. The polymorphisms rs6502051 and rs4246444 were associated with lower levels of 14:1n-5, 16:1n-7, and 18:1n-9. Blood levels of 16:1n-7 were associated with higher prostate cancer incidence, with rate ratios for men in increasing quintiles of 1.00, 1.40, 1.35, 1.44, and 1.97 (95 confidence interval: 1.273.06; P-trend 0.003). Furthermore, 16:1n-7 levels were positively related to incidence of high-grade (Gleason score 7) tumors (rate ratio(Q5Q1) 3.92; 95 confidence interval: 1.728.94) but not low-grade tumors (rate ratio(Q5Q1) 1.51; 95 confidence interval: 0.872.62) (P-heterogeneity 0.02). Higher activity of enzymes involved in de novo lipogenesis, as reflected in blood levels of 16:1n-7, could be involved in the development of high-grade prostate cancer.
引用
收藏
页码:1246 / 1255
页数:10
相关论文
共 41 条
[1]  
American Cancer Society, 2012, CANC FACTS FIG 2012, P19
[2]   FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis [J].
Bandyopadhyay, S ;
Pai, SK ;
Watabe, M ;
Gross, SC ;
Hirota, S ;
Hosobe, S ;
Tsukada, T ;
Miura, K ;
Saito, K ;
Markwell, SJ ;
Wang, Y ;
Huggenvik, J ;
Pauza, ME ;
Iiizumi, M ;
Watabe, K .
ONCOGENE, 2005, 24 (34) :5389-5395
[3]   Fasting whole blood as a biomarker of essential fatty acid intake in epidemiologic studies: Comparison with adipose tissue and plasma [J].
Baylin, A ;
Kim, MK ;
Donovan-Palmer, A ;
Siles, X ;
Dougherty, L ;
Tocco, P ;
Campos, H .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2005, 162 (04) :373-381
[4]   RNA interference-mediated silencing of the Acetyl-CoA-Carboxylase-α gene induces growth inhibition and apoptosis of prostate cancer cells [J].
Brusselmans, K ;
De Schrijver, E ;
Verhoeven, G ;
Swinnen, JV .
CANCER RESEARCH, 2005, 65 (15) :6719-6725
[5]   Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism [J].
Cao, Haiming ;
Gerhold, Kristin ;
Mayers, Jared R. ;
Wiest, Michelle M. ;
Watkins, Steven M. ;
Hotamisligil, Goekhan S. .
CELL, 2008, 134 (06) :933-944
[6]   A prospective study of trans-fatty acid levels in blood and risk of prostate cancer [J].
Chavarro, Jorge E. ;
Stampfer, Meir J. ;
Campos, Hannia ;
Kurth, Tobias ;
Willett, Walter C. ;
Ma, Jing .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2008, 17 (01) :95-101
[7]   A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk [J].
Chavarro, Jorge E. ;
Stampfer, Meir J. ;
Li, Haojie ;
Campos, Hannia ;
Kurth, Tobias ;
Ma, Jing .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (07) :1364-1370
[8]   Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition [J].
Crowe, Francesca L. ;
Allen, Naomi E. ;
Appleby, Paul N. ;
Overvad, Kim ;
Aardestrup, Inge V. ;
Johnsen, Nina F. ;
Tjonneland, Anne ;
Linseisen, Jakob ;
Kaaks, Rudolf ;
Boeing, Heiner ;
Kroeger, Janine ;
Trichopoulou, Antonia ;
Zavitsanou, Assimina ;
Trichopoulos, Dimitrios ;
Sacerdote, Carlotta ;
Palli, Domenico ;
Tumino, Rosario ;
Agnoli, Claudia ;
Kiemeney, Lambertus A. ;
Bueno-de-Mesquita, H. Bas ;
Chirlaque, Maria-Dolores ;
Ardanaz, Eva ;
Larranaga, Nerea ;
Quiros, Jose R. ;
Sanchez, Maria-Jose ;
Gonzalez, Carlos A. ;
Stattin, Paer ;
Hallmans, Goeran ;
Bingham, Sheila ;
Khaw, Kay-Tee ;
Rinaldi, Sabina ;
Slimani, Nadia ;
Jenab, Mazda ;
Riboli, Elio ;
Key, Timothy J. .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2008, 88 (05) :1353-1363
[9]  
De Schrijver E, 2003, CANCER RES, V63, P3799
[10]   PROSPECTIVE-STUDY OF PLASMA FATTY-ACIDS AND RISK OF PROSTATE-CANCER [J].
GANN, PH ;
HENNEKENS, CH ;
SACKS, FM ;
GRODSTEIN, F ;
GIOVANNUCCI, EL ;
STAMPFER, MJ .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (04) :281-286