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Grant Details

Grant Number: 5P01CA087969-13 Interpret this number
Primary Investigator: Stampfer, Meir
Organization: Brigham And Women'S Hospital
Project Title: Dietary and Hormonal Determinants of Cancer in Women
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): The long-term objective of this Program Project is to identify novel hormonal, dietary and genetic determinants of cancer risk (specifically breast, colorectal, and ovarian cancers) in v\/omen, with the aim of finding means for prevention and improved survival. The availability of questionnaire data, blood and urine samples and paraffin-embedded tumor tissue, coupled with up to 36 years follow-up, affords the opportunity to further understand the time course, as well as mechanisms of cancer development. Cross-cutting themes include the investigation of vitamin D and melatonin, energy balance and inflammatory pathways, as well as the examination of fatal outcomes and the molecular characterization of tumors. In Project 1, we will examine vitamin D, melatonin, and dietary intake (including 1-carbon nutrients and change in alcohol intake) in relation to breast cancer risk; further, risk factors for clinically relevant tumor subtypes and fatal disease will be assessed. We will assess the contribution of modifiable factors to incidence in women at high genetic risk. Further the role of energy balance in survival will be assessed. In Project 2, we will assess vitamin D and melatonin, including associations with tumor characteristics. The roles of insulin, adiponectin and insulin-like growth factors as well as inflammation markers in colon cancer incidence and survival will be assessed, in Project 3, we will evaluate vitamin D, melatonin, dietary factors (flavonoids, lactose and acrylamide) and plasma markers of inflammation in relation to ovarian cancer risk. Further, we will assess tumor markers in relation to ovarian cancer risk factors, as well as risk factors for fatal disease. In Project 4, we will extend and apply analytic methods that will improve our modeling of cumulative exposures that influence risk at different times in life, extend polytomous logistic regression models in a complex tumor biomarker setting, and improve evaluation of breast and colon cancer risk prediction models. This application is based on the Nurses' Health Study cohort, comprising 121,700 women who were 30 to 55 years of age in 1976. Through funding of the Cores, we maintain follow-up of the cohort and confirmation of incident cancers and deaths, oversee acquisition and use of biomarkers and provide leadership and data analysis. The Nurses' Health Study as funded through this Program Project contributes to the NCI sponsored Cohort Consortium, belongs to 12 other consortia and has served as the research platform for over 30 outside collaborators over the last 5 years.

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Publications

Prediction of breast cancer risk based on profiling with common genetic variants.
Authors: Mavaddat N, Pharoah PD, Michailidou K, Tyrer J, Brook MN, Bolla MK, Wang Q, Dennis J, Dunning AM, Shah M, Luben R, Brown J, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Czene K, Darabi H, Eriksson M, Peto J, Dos-Santos-Silva I, Dudbridge F, Johnson N, Schmidt MK, Broeks A, Verhoef S, Rutgers EJ, Swerdlow A, Ashworth A, Orr N, Schoemaker MJ, Figueroa J, Chanock SJ, Brinton L, Lissowska J, Couch FJ, Olson JE, Vachon C, Pankratz VS, Lambrechts D, Wildiers H, Van Ongeval C, van Limbergen E, Kristensen V, Grenaker Alnæs G, Nord S, Borresen-Dale AL, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Burwinkel B, Marme F, Schneeweiss A, Sohn C, Trentham-Dietz A, Newcomb P, Titus L, Egan KM, Hunter DJ, Lindstrom S, Tamimi RM, Kraft P, Rahman N, Turnbull C, Renwick A, Seal S, Li J, Liu J, Humphreys K, Benitez J, Pilar Zamora M, Arias Perez JI, Menéndez P, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Bogdanova NV, Antonenkova NN, Dörk T, Anton-Culver H, Neuhausen SL, Ziogas A, Bernstein L, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Cox A, Cross SS, Reed MW, Khusnutdinova E, Bermisheva M, Prokofyeva D, Takhirova Z, Meindl A, Schmutzler RK, Sutter C, Yang R, Schürmann P, Bremer M, Christiansen H, Park-Simon TW, Hillemanns P, Guénel P, Truong T, Menegaux F, Sanchez M, Radice P, Peterlongo P, Manoukian S, Pensotti V, Hopper JL, Tsimiklis H, Apicella C, Southey MC, Brauch H, Brüning T, Ko YD, Sigurdson AJ, Doody MM, Hamann U, Torres D, Ulmer HU, Försti A, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Andrulis IL, Knight JA, Glendon G, Marie Mulligan A, Chenevix-Trench G, Balleine R, Giles GG, Milne RL, McLean C, Lindblom A, Margolin S, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Eilber U, Wang-Gohrke S, Hooning MJ, Hollestelle A, van den Ouweland AM, Koppert LB, Carpenter J, Clarke C, Scott R, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Brenner H, Arndt V, Stegmaier C, Karina Dieffenbach A, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Offit K, Vijai J, Robson M, Rau-Murthy R, Dwek M, Swann R, Annie Perkins K, Goldberg MS, Labrèche F, Dumont M, Eccles DM, Tapper WJ, Rafiq S, John EM, Whittemore AS, Slager S, Yannoukakos D, Toland AE, Yao S, Zheng W, Halverson SL, González-Neira A, Pita G, Rosario Alonso M, Álvarez N, Herrero D, Tessier DC, Vincent D, Bacot F, Luccarini C, Baynes C, Ahmed S, Maranian M, Healey CS, Simard J, Hall P, Easton DF, Garcia-Closas M
Source: J Natl Cancer Inst, 2015 May;107(5), p. null.
EPub date: 2015 Apr 8.
PMID: 25855707
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Marine ?-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability.
Authors: Song M, Nishihara R, Wu K, Qian ZR, Kim SA, Sukawa Y, Mima K, Inamura K, Masuda A, Yang J, Fuchs CS, Giovannucci EL, Ogino S, Chan AT
Source: J Natl Cancer Inst, 2015 Apr;107(4), p. null.
EPub date: 2015 Mar 25.
PMID: 25810492
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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
Authors: Zimmermann E, Ängquist LH, Mirza SS, Zhao JH, Chasman DI, Fischer K, Qi Q, Smith AV, Thinggaard M, Jarczok MN, Nalls MA, Trompet S, Timpson NJ, Schmidt B, Jackson AU, Lyytikäinen LP, Verweij N, Mueller-Nurasyid M, Vikström M, Marques-Vidal P, Wong A, Meidtner K, Middelberg RP, Strawbridge RJ, Christiansen L, FTO-Mortality Collaborating Group, Kyvik KO, Hamsten A, Jääskeläinen T, Tjønneland A, Eriksson JG, Whitfield JB, Boeing H, Hardy R, Vollenweider P, Leander K, Peters A, van der Harst P, Kumari M, Lehtimäki T, Meirhaeghe A, Tuomilehto J, Jöckel KH, Ben-Shlomo Y, Sattar N, Baumeister SE, Davey Smith G, Casas JP, Houston DK, März W, Christensen K, Gudnason V, Hu FB, Metspalu A, Ridker PM, Wareham NJ, Loos RJ, Tiemeier H, Sonestedt E, Sørensen TI
Source: Obes Rev, 2015 Apr;16(4), p. 327-40.
EPub date: 2015 Mar 5.
PMID: 25752329
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Antihypertensive medication use and incident breast cancer in women.
Authors: Devore EE, Kim S, Ramin CA, Wegrzyn LR, Massa J, Holmes MD, Michels KB, Tamimi RM, Forman JP, Schernhammer ES
Source: Breast Cancer Res Treat, 2015 Feb;150(1), p. 219-29.
EPub date: 2015 Feb 21.
PMID: 25701121
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Investigation of dietary factors and endometrial cancer risk using a nutrient-wide association study approach in the EPIC and Nurses' Health Study (NHS) and NHSII.
Authors: Merritt MA, Tzoulaki I, Tworoger SS, De Vivo I, Hankinson SE, Fernandes J, Tsilidis KK, Weiderpass E, Tjønneland A, Petersen KE, Dahm CC, Overvad K, Dossus L, Boutron-Ruault MC, Fagherazzi G, Fortner RT, Kaaks R, Aleksandrova K, Boeing H, Trichopoulou A, Bamia C, Trichopoulos D, Palli D, Grioni S, Tumino R, Sacerdote C, Mattiello A, Bueno-de-Mesquita HB, Onland-Moret NC, Peeters PH, Gram IT, Skeie G, Quirós JR, Duell EJ, Sánchez MJ, Salmerón D, Barricarte A, Chamosa S, Ericson U, Sonestedt E, Nilsson LM, Idahl A, Khaw KT, Wareham N, Travis RC, Rinaldi S, Romieu I, Patel CJ, Riboli E, Gunter MJ
Source: Cancer Epidemiol Biomarkers Prev, 2015 Feb;24(2), p. 466-71.
PMID: 25662427
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