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Grant Details

Grant Number: 5U19CA055075-20 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard School Of Public Health
Project Title: Prospective Studies of Diet and Cancer in Men and Women
Fiscal Year: 2011
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Abstract

DESCRIPTION (provided by applicant): This proposed continuing Program Project will use prospectively collected dietary data, frozen plasma and DNA, and tumor tissue to address hypotheses regarding cancers of the prostate, colon and rectum, breast, and brain (glioma). This Program supports, and depends on, the continued follow-up of 51,529 men who have completed extensive dietary questionnaires every four years since 1986 (the Health Professionals Follow-up Study, HPFS), and is also closely linked to the Nurses' Health Study (NHS) of 121,700 women. The Program Project is a founding member of, and contributes data and DNA samples to; the NCI sponsored Cohort Consortium on genetic determinants of cancer risk. The proposed continuation will extend and refine observations from the first 19 years of follow-up and will also address new hypotheses related to both cancer incidence and survival. Cross-cutting themes are the investigation of vitamin D, inflammatory, and energy balance pathways as they relate to cancer incidence. Particular emphasis is given to potentially modifiable determinants of cancer risk and survival. Project 1 examines hypotheses relating vitamin D intakes, blood levels, and metabolizing genes and consumption of dairy products to both localized and fatal prostate cancer. Use of statins, aspirin, and NSAID's and of insulinemia (weight and weight gain, dietary insulin index, plasma C-peptide, and adiponectin) will also be examined detail. Specific dietary factors will be addressed in relation to survival among men with prostate cancer. Project 2 examines vitamin D blood levels, intakes, and metabolizing genes in relation to the diagnosis of colorectal cancer and adenomas, including associations with histological and molecular characteristics of tumors. The use of anti-inflammatory agents and their interactions with polymorphisms in related genes, and of insulin, adiponectin, and IFG-1 pathways to risk of risk of colon cancer will also be evaluated. Specific dietary factors, weight change, physical activity, and use of anti-inflammatory agents will be examined in relation to survival among patients with colorectal cancer. Project 3 pools data from 21 major prospective studies of diet and cancer. Precise and unique information has already been obtained for breast, lung, colon, kidney, ovarian, and pancreatic cancer, and the proposed work will extend analyses to prostate cancer, estrogen receptor negative breast cancer, and gliomas. Project 4 addresses methodological issues in epidemiological studies of genetic polymorphisms, diet and risk of cancer. These include the analysis of multiple polymorphisms within metabolic pathways and the effects of, and adjustment for, measurement errors in both diet and genotypes. Lav summary: These highly interrelated projects integrate dietary factors, related non-dietary factors, blood nutrient and hormone levels, genetic susceptibility, and molecular characteristics of tumors. The findings will contribute importantly to the prevention and prognosis of major cancers of men and women.

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Publications

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Authors: Holmes MV, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, Prieto-Merino D, Dehghan A, Trompet S, Wong A, Cavadino A, Drogan D, Padmanabhan S, Li S, Yesupriya A, Leusink M, Sundstrom J, Hubacek JA, Pikhart H, Swerdlow DI, Panayiotou AG, Borinskaya SA, Finan C, Shah S, Kuchenbaecker KB, Shah T, Engmann J, Folkersen L, Eriksson P, Ricceri F, Melander O, Sacerdote C, Gamble DM, Rayaprolu S, Ross OA, McLachlan S, Vikhireva O, Sluijs I, Scott RA, Adamkova V, Flicker L, Bockxmeer FM, Power C, Marques-Vidal P, Meade T, Marmot MG, Ferro JM, Paulos-Pinheiro S, Humphries SE, Talmud PJ, Mateo Leach I, Verweij N, Linneberg A, Skaaby T, Doevendans PA, Cramer MJ, van der Harst P, Klungel OH, Dowling NF, Dominiczak AF, Kumari M, Nicolaides AN, Weikert C, Boeing H, Ebrahim S, Gaunt TR, Price JF, Lannfelt L, Peasey A, Kubinova R, Pajak A, Malyutina S, Voevoda MI, Tamosiunas A, Maitland-van der Zee AH, Norman PE, Hankey GJ, Bergmann MM, Hofman A, Franco OH, Cooper J, Palmen J, Spiering W, de Jong PA, Kuh D, Hardy R, Uitterlinden AG, Ikram MA, Ford I, Hyppönen E, Almeida OP, Wareham NJ, Khaw KT, Hamsten A, Husemoen LL, Tjønneland A, Tolstrup JS, Rimm E, Beulens JW, Verschuren WM, Onland-Moret NC, Hofker MH, Wannamethee SG, Whincup PH, Morris R, Vicente AM, Watkins H, Farrall M, Jukema JW, Meschia J, Cupples LA, Sharp SJ, Fornage M, Kooperberg C, LaCroix AZ, Dai JY, Lanktree MB, Siscovick DS, Jorgenson E, Spring B, Coresh J, Li YR, Buxbaum SG, Schreiner PJ, Ellison RC, Tsai MY, Patel SR, Redline S, Johnson AD, Hoogeveen RC, Hakonarson H, Rotter JI, Boerwinkle E, de Bakker PI, Kivimaki M, Asselbergs FW, Sattar N, Lawlor DA, Whittaker J, Davey Smith G, Mukamal K, Psaty BM, Wilson JG, Lange LA, Hamidovic A, Hingorani AD, Nordestgaard BG, Bobak M, Leon DA, Langenberg C, Palmer TM, Reiner AP, Keating BJ, Dudbridge F, Casas JP, InterAct Consortium
Source: BMJ, 2014 Jul 10;349, p. g4164.
EPub date: 2014 Jul 10.
PMID: 25011450
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Plasma levels of fetuin-A and risk of coronary heart disease in US women: the Nurses' Health Study.
Authors: Sun Q, Jiménez MC, Townsend MK, Rimm EB, Manson JE, Albert CM, Rexrode KM
Source: J Am Heart Assoc, 2014 Jun 24;3(3), p. e000939.
EPub date: 2014 Jun 24.
PMID: 24963103
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Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.
Authors: Imamura Y, Lochhead P, Yamauchi M, Kuchiba A, Qian ZR, Liao X, Nishihara R, Jung S, Wu K, Nosho K, Wang YE, Peng S, Bass AJ, Haigis KM, Meyerhardt JA, Chan AT, Fuchs CS, Ogino S
Source: Mol Cancer, 2014 May 31;13, p. 135.
EPub date: 2014 May 31.
PMID: 24885062
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Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.
Authors: Bezawada N, Song M, Wu K, Mehta RS, Milne GL, Ogino S, Fuchs CS, Giovannucci EL, Chan AT
Source: Cancer Prev Res (Phila), 2014 Jul;7(7), p. 758-65.
EPub date: 2014 May 13.
PMID: 24824037
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Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study.
Authors: Li S, Flint A, Pai JK, Forman JP, Hu FB, Willett WC, Rexrode KM, Mukamal KJ, Rimm EB
Source: BMJ, 2014 Apr 29;348, p. g2659.
EPub date: 2014 Apr 29.
PMID: 24782515
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Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD).
Authors: Fink SP, Yamauchi M, Nishihara R, Jung S, Kuchiba A, Wu K, Cho E, Giovannucci E, Fuchs CS, Ogino S, Markowitz SD, Chan AT
Source: Sci Transl Med, 2014 Apr 23;6(233), p. 233re2.
PMID: 24760190
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Association of C-peptide and leptin with prostate cancer incidence in the Health Professionals Follow-up Study.
Authors: Lai GY, Giovannucci EL, Pollak MN, Peskoe SB, Stampfer MJ, Willett WC, Platz EA
Source: Cancer Causes Control, 2014 May;25(5), p. 625-32.
EPub date: 2014 Mar 25.
PMID: 24664287
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