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Grant Details

Grant Number: 5U19CA055075-20 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard University (Sch Of Public Hlth)
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

Total calcium intake and colorectal adenoma in young women.
Authors: Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL
Source: Cancer Causes Control, 2014 Apr;25(4), p. 451-60.
EPub date: 2014 Feb 22.
PMID: 24562904
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Body-mass index and mortality among adults with incident type 2 diabetes.
Authors: Tobias DK, Pan A, Jackson CL, O'Reilly EJ, Ding EL, Willett WC, Manson JE, Hu FB
Source: N Engl J Med, 2014 Jan 16;370(3), p. 233-44.
PMID: 24428469
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Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.
Authors: Lemaitre RN, Johnson CO, Hesselson S, Sotoodhenia N, McKnight B, Sitlani CM, Rea TD, King IB, Kwok PY, Mak A, Li G, Brody J, Larson E, Mozaffarian D, Psaty BM, Huertas-Vazquez A, Tardif JC, Albert CM, Lyytikäinen LP, Arking DE, Kääb S, Huikuri HV, Krijthe BP, Eijgelsheim M, Wang YA, Reinier K, Lehtimäki T, Pulit SL, Brugada R, Müller-Nurasyid M, Newton-Cheh CH, Karhunen PJ, Stricker BH, Goyette P, Rotter JI, Chugh SS, Chakravarti A, Jouven X, Siscovick DS
Source: Heart Rhythm, 2014 Mar;11(3), p. 471-7.
EPub date: 2014 Jan 10.
PMID: 24418166
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Use of systems biology approaches to analysis of genome-wide association studies of myocardial infarction and blood cholesterol in the nurses' health study and health professionals' follow-up study.
Authors: Reilly D, Hao K, Jensen MK, Girman CJ, Rimm EB
Source: PLoS One, 2013;8(12), p. e85369.
EPub date: 2013 Dec 26.
PMID: 24386469
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Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.
Authors: Pettersson A, Lis RT, Meisner A, Flavin R, Stack EC, Fiorentino M, Finn S, Graff RE, Penney KL, Rider JR, Nuttall EJ, Martin NE, Sesso HD, Pollak M, Stampfer MJ, Kantoff PW, Giovannucci EL, Loda M, Mucci LA
Source: J Natl Cancer Inst, 2013 Dec 18;105(24), p. 1881-90.
EPub date: 2013 Nov 30.
PMID: 24292212
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Long-term use of multivitamins and risk of colorectal adenoma in women.
Authors: Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL
Source: Br J Cancer, 2014 Jan 7;110(1), p. 249-55.
EPub date: 2013 Nov 12.
PMID: 24220696
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