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Grant Details

Grant Number: 5R01CA050385-25 Interpret this number
Primary Investigator: Willett, Walter
Organization: Harvard School Of Public Health
Project Title: Risk Factors for Breast Cancer in Younger Nurses
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): We propose to continue the follow-up of 116,678 women who in 1989 were enrolled in the prospective Nurses' Health Study II (NHSII) to identify potentially modifiable determinants of breast cancer risk in young women. In this unique cohort, exposure information has been collected at two-year intervals beginning when women were 25-42 years of age. Active response to follow-up questionnaires has been approximately 90% and ascertainment of deaths is virtually complete; through 2011 we expect 4023 incident cases of invasive breast cancer. Since 1989, we have collected plasma, DNA, red blood cells, and urine samples from participants; already these resources have provided many new insights on factors that influence the incidence of premenopausal breast cancer. Our proposed specific aims build upon the extensive exposure information collected during premenopausal years and substantially extend the original objectives. Specifically, we will evaluate whether associations we have seen with high school and premenopausal adult diet, adolescent physical activity, shift work, and melatonin secretion also influence risk of postmenopausal breast cancer. To assess potential underlying mechanisms for an association we observed with consumption of red meat, we will evaluate the relation of plasma ferritin to risk of breast cancer. Further we will assess whether specific carotenoids, and plasma enterolactone predict risk. We will also evaluate whether the associations that we observe between modifiable factors and risk of breast cancer are accounted for by increased mammographic density. We will use emerging results from genome wide association studies (GWAS) to construct a genetic risk score based on the collective effects of multiple polymorphisms with established links to breast cancer; among women at higher genetic risk we evaluate the potential for risk reduction by the modifiable risk factors that we have identified. We will also use the information on traditional and novel risk factors, plasma hormone levels, mammographic density, and the genetic risk score that will be available in NHSII to create a new prediction model for premenopausal breast cancer specifically and also for postmenopausal breast cancer using exposures ascertained before menopause in addition to traditional risk factors determined after menopause. This breadth of information should substantially outperform available models and identify individual women at high risk for focused research and, potentially, preventive interventions. The results of the proposed aims will continue to provide new information on the origins of premenopausal and postmenopausal breast cancer; and on modifiable risk factors. In addition to these specific aims, the follow-up of the NHSII cohort provides a key source of data and biological specimens from young women that are used by multiple consortia and collaborations, and that provide the foundation for many ancillary studies related to women's health.

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Publications

Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts.
Authors: Muraki I, Wu H, Imamura F, Laden F, Rimm EB, Hu FB, Willett WC, Sun Q
Source: Am J Clin Nutr, 2015 Jan;101(1), p. 164-72.
EPub date: 2014 Nov 12.
PMID: 25527760
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Caffeine intake and the risk of kidney stones.
Authors: Ferraro PM, Taylor EN, Gambaro G, Curhan GC
Source: Am J Clin Nutr, 2014 Dec;100(6), p. 1596-603.
EPub date: 2014 Oct 1.
PMID: 25411295
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MicroRNA related polymorphisms and breast cancer risk.
Authors: Khan S, Greco D, Michailidou K, Milne RL, Muranen TA, Heikkinen T, Aaltonen K, Dennis J, Bolla MK, Liu J, Hall P, Irwanto A, Humphreys K, Li J, Czene K, Chang-Claude J, Hein R, Rudolph A, Seibold P, Flesch-Janys D, Fletcher O, Peto J, dos Santos Silva I, Johnson N, Gibson L, Aitken Z, Hopper JL, Tsimiklis H, Bui M, Makalic E, Schmidt DF, Southey MC, Apicella C, Stone J, Waisfisz Q, Meijers-Heijboer H, Adank MA, van der Luijt RB, Meindl A, Schmutzler RK, Müller-Myhsok B, Lichtner P, Turnbull C, Rahman N, Chanock SJ, Hunter DJ, Cox A, Cross SS, Reed MW, Schmidt MK, Broeks A, Van't Veer LJ, Hogervorst FB, Fasching PA, Schrauder MG, Ekici AB, Beckmann MW, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Benitez J, Zamora PM, Perez JI, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Pharoah PD, Dunning AM, Shah M, Luben R, Brown J, Couch FJ, Wang X, Vachon C, Olson JE, Lambrechts D, Moisse M, Paridaens R, Christiaens MR, Guénel P, Truong T, Laurent-Puig P, Mulot C, Marme F, Burwinkel B, Schneeweiss A, Sohn C, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Andrulis IL, Knight JA, Tchatchou S, Mulligan AM, Dörk T, Bogdanova NV, Antonenkova NN, Anton-Culver H, Darabi H, Eriksson M, Garcia-Closas M, Figueroa J, Lissowska J, Brinton L, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Kristensen VN, kConFab Investigators, Australian Ovarian Cancer Study Group, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Lindblom A, Margolin S, Radice P, Peterlongo P, Barile M, Mariani P, Hooning MJ, Martens JW, Collée JM, Jager A, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Giles GG, McLean C, Brauch H, Brüning T, Ko YD, GENICA Network, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Swerdlow A, Ashworth A, Orr N, Jones M, Simard J, Goldberg MS, Labrčche F, Dumont M, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Kataja V, Kosma VM, Hartikainen JM, Mannermaa A, Hamann U, Chenevix-Trench G, Blomqvist C, Aittomäki K, Easton DF, Nevanlinna H
Source: PLoS One, 2014;9(11), p. e109973.
EPub date: 2014 Nov 12.
PMID: 25390939
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Pre-pregnancy fried food consumption and the risk of gestational diabetes mellitus: a prospective cohort study.
Authors: Bao W, Tobias DK, Olsen SF, Zhang C
Source: Diabetologia, 2014 Dec;57(12), p. 2485-91.
EPub date: 2014 Oct 11.
PMID: 25303998
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Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study.
Authors: Zhang C, Tobias DK, Chavarro JE, Bao W, Wang D, Ley SH, Hu FB
Source: BMJ, 2014 Sep 30;349, p. g5450.
EPub date: 2014 Sep 30.
PMID: 25269649
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Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.
Authors: Lin WY, Camp NJ, Ghoussaini M, Beesley J, Michailidou K, Hopper JL, Apicella C, Southey MC, Stone J, Schmidt MK, Broeks A, Van't Veer LJ, Th Rutgers EJ, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Bolla MK, Wang Q, Dennis J, Sawyer EJ, Cheng T, Tomlinson I, Kerin MJ, Miller N, Marmé F, Surowy HM, Burwinkel B, Guénel P, Truong T, Menegaux F, Mulot C, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Benitez J, Zamora MP, Arias Perez JI, Menéndez P, González-Neira A, Pita G, Alonso MR, Alvarez N, Herrero D, Anton-Culver H, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Müller-Myhsok B, Brauch H, Brüning T, Ko YD, GENICA Network, Tessier DC, Vincent D, Bacot F, Nevanlinna H, Aittomäki K, Blomqvist C, Khan S, Matsuo K, Ito H, Iwata H, Horio A, Bogdanova NV, Antonenkova NN, Dörk T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, kConFab Investigators, Australian Ovarian Cancer Study Group, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Neven P, Wauters E, Wildiers H, Lambrechts D, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Radice P, Peterlongo P, Manoukian S, Bonanni B, Couch FJ, Wang X, Vachon C, Purrington K, Giles GG, Milne RL, Mclean C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labrčche F, Dumont M, Teo SH, Yip CH, Hassan N, Vithana EN, Kristensen V, Zheng W, Deming-Halverson S, Shrubsole MJ, Long J, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Devilee P, Tollenaar RA, Seynaeve C, Van Asperen CJ, García-Closas M, Figueroa J, Lissowska J, Brinton L, Czene K, Darabi H, Eriksson M, Brand JS, Hooning MJ, Hollestelle A, Van Den Ouweland AM, Jager A, Li J, Liu J, Humphreys K, Shu XO, Lu W, Gao YT, Cai H, Cross SS, Reed MW, Blot W, Signorello LB, Cai Q, Pharoah PD, Perkins B, Shah M, Blows FM, Kang D, Yoo KY, Noh DY, Hartman M, Miao H, Chia KS, Putti TC, Hamann U, Luccarini C, Baynes C, Ahmed S, Maranian M, Healey CS, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Sangrajrang S, Gaborieau V, Brennan P, Mckay J, Slager S, Toland AE, Yannoukakos D, Shen CY, Hsiung CN, Wu PE, Ding SL, Ashworth A, Jones M, Orr N, Swerdlow AJ, Tsimiklis H, Makalic E, Schmidt DF, Bui QM, Chanock SJ, Hunter DJ, Hein R, Dahmen N, Beckmann L, Aaltonen K, Muranen TA, Heikkinen T, Irwanto A, Rahman N, Turnbull CA, Breast and Ovarian Cancer Susceptibility (BOCS) Study, Waisfisz Q, Meijers-Heijboer HE, Adank MA, Van Der Luijt RB, Hall P, Chenevix-Trench G, Dunning A, Easton DF, Cox A
Source: Hum Mol Genet, 2015 Jan 1;24(1), p. 285-98.
EPub date: 2014 Aug 28.
PMID: 25168388
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Parental social responsiveness and risk of autism spectrum disorder in offspring.
Authors: Lyall K, Constantino JN, Weisskopf MG, Roberts AL, Ascherio A, Santangelo SL
Source: JAMA Psychiatry, 2014 Aug;71(8), p. 936-42.
PMID: 25100167
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Being overweight or obese and risk of developing rheumatoid arthritis among women: a prospective cohort study.
Authors: Lu B, Hiraki LT, Sparks JA, Malspeis S, Chen CY, Awosogba JA, Arkema EV, Costenbader KH, Karlson EW
Source: Ann Rheum Dis, 2014 Nov;73(11), p. 1914-22.
EPub date: 2014 Jul 23.
PMID: 25057178
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