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Grant Details

Grant Number: 5R01CA098661-10 Interpret this number
Primary Investigator: Zeleniuch-Jacquotte, Anne
Organization: New York University School Of Medicine
Project Title: Vitamin D, Related Genes and Breast Cancer Risk
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by investigator): A large body of experimental data indicates that vitamin D inhibits cellular proliferation and induces differentiation and apoptosis, suggesting a protective effect against cancer. The enzymes coding for the formation and degradation of 1,25(OH)2D, the active metabolite of vitamin D, are present in both normal and cancer breast cells, as is the vitamin D receptor, a key mediator in the vitamin D pathway. Ecological and case- control studies support a protective role of vitamin D against breast cancer; however, prospective data are sparse. Moreover, few studies have measured circulating 25(OH)D which is considered the best indicator of vitamin D status because it captures both the absorption of vitamin D in the intestine and its production in the skin. We propose to conduct a comprehensive study of the vitamin D pathway in relation to breast cancer risk. Because vitamin D impacts cell proliferation, the main mechanism by which estrogens increase breast cancer risk, we will also assess whether vitamin D modifies the association of circulating estradiol with breast cancer risk in postmenopausal women. The study will be a case-control study nested within two cohorts, the NYU Women's Health Study and the Mammary Screening Cohort in Sweden. These two cohorts have a similar design and collected biological samples prospectively. A total of 1,995 incident cases is expected to be observed within these two cohorts. One (or two for cases d 52 years of age) control(s) will be selected for each case, matching the case on cohort, race/ethnicity, menopausal status, age at, and date of, blood donation. In addition to baseline measurements, we will assess 25(OH)D at repeat points in time in about 50 percent of the matched sets (2 samples in 25 percent and 3 samples in 25 percent). We will also assess genetic variation in vitamin D-related genes (CYP27A1, CYP24A1, DBP, VDR, and RXRA) and evaluate the joint effects of circulating 25(OH)D and variants in these genes on breast cancer risk. Circulating levels of estradiol will be measured in postmenopausal matched sets.

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Publications

Circulating cytokines and risk of B-cell non-Hodgkin lymphoma: a prospective study.
Authors: Gu Y, Shore RE, Arslan AA, Koenig KL, Liu M, Ibrahim S, Lokshin AE, Zeleniuch-Jacquotte A
Source: Cancer Causes Control, 2010 Aug;21(8), p. 1323-33.
EPub date: 2010 Apr 7.
PMID: 20373009
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Reproducibility of serum cytokines and growth factors.
Authors: Gu Y, Zeleniuch-Jacquotte A, Linkov F, Koenig KL, Liu M, Velikokhatnaya L, Shore RE, Marrangoni A, Toniolo P, Lokshin AE, Arslan AA
Source: Cytokine, 2009 Jan;45(1), p. 44-9.
EPub date: 2008 Dec 5.
PMID: 19058974
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Reproducibility of serum pituitary hormones in women.
Authors: Arslan AA, Gu Y, Zeleniuch-Jacquotte A, Koenig KL, Liu M, Velikokhatnaya L, Shore RE, Toniolo P, Linkov F, Lokshin AE
Source: Cancer Epidemiol Biomarkers Prev, 2008 Aug;17(8), p. 1880-3.
PMID: 18708375
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Reliability of tumor markers, chemokines, and metastasis-related molecules in serum.
Authors: Linkov F, Gu Y, Arslan AA, Liu M, Shore RE, Velikokhatnaya L, Koenig KL, Toniolo P, Marrangoni A, Yurkovetsky Z, Zeleniuch-Jacquotte A, Lokshin AE
Source: Eur Cytokine Netw, 2009 Mar;20(1), p. 21-6.
PMID: 19318317
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Reliability of serum assays of iron status in postmenopausal women.
Authors: Zeleniuch-Jacquotte A, Zhang Q, Dai J, Shore RE, Arslan AA, Koenig KL, Karkoszka J, Afanasyeva Y, Frenkel K, Toniolo P, Huang X
Source: Ann Epidemiol, 2007 May;17(5), p. 354-8.
EPub date: 2006 Oct 5.
PMID: 17027294
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