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Grant Details

Grant Number: 5R01CA050385-24 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: 2012
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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. PUBLIC HEALTH RELEVANCE: We propose to continue the follow-up of 116,678 women, initially 25 to 42 years of age when recruited in 1989, in the Nurses' Health Study II. We will assess the risk of breast cancer in pre and post menopausal women through an evaluation of dietary and lifestyle factors during adolescence and early adult life, biomarkers that reflect dietary factors, mammographic density, and a new genetic risk score. Already, this study has identified multiple potentially modifiable risk factors for breast cancer in young women, and the extended follow-up should provide further information on the prevention of this and other important diseases.

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Publications

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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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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Sugar-sweetened soda consumption and risk of developing rheumatoid arthritis in women.
Authors: Hu Y, Costenbader KH, Gao X, Al-Daabil M, Sparks JA, Solomon DH, Hu FB, Karlson EW, Lu B
Source: Am J Clin Nutr, 2014 Sep;100(3), p. 959-67.
EPub date: 2014 Jul 16.
PMID: 25030783
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Invasive cutaneous squamous cell carcinoma incidence in US health care workers.
Authors: Nguyen KD, Han J, Li T, Qureshi AA
Source: Arch Dermatol Res, 2014 Aug;306(6), p. 555-60.
EPub date: 2014 May 28.
PMID: 24866765
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Application of the Rosner-Wei risk-prediction model to estimate sexual orientation patterns in colon cancer risk in a prospective cohort of US women.
Authors: Austin SB, Pazaris MJ, Wei EK, Rosner B, Kennedy GA, Bowen D, Spiegelman D
Source: Cancer Causes Control, 2014 Aug;25(8), p. 999-1006.
EPub date: 2014 May 23.
PMID: 24852207
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Physical activity and sedentary behaviors associated with risk of progression from gestational diabetes mellitus to type 2 diabetes mellitus: a prospective cohort study.
Authors: Bao W, Tobias DK, Bowers K, Chavarro J, Vaag A, Grunnet LG, StrÝm M, Mills J, Liu A, Kiely M, Zhang C
Source: JAMA Intern Med, 2014 Jul;174(7), p. 1047-55.
PMID: 24841449
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