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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA114329-04 Interpret this number
Primary Investigator: Toniolo, Paolo
Organization: New York University School Of Medicine
Project Title: Pregnancy Hormones and Risk of Maternal Breast Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): First full-term pregnancies occurring early in life, afford the mother a substantial lifetime protection from breast cancer. The reasons for such protection are unknown, but many experimental observations in rodents suggest that the prolonged elevation in specific circulating hormones in pregnancy play a fundamental role in mammary proliferation and differentiation and reduce the effects of carcinogenic insults. In a case-control study (1890 cases, 3780 controls) nested within two large cohorts in Finland and Sweden totaling over 1.2 million subjects we will explore putative associations between circulating concentrations of a panel of endogenous hormones measured in stored specimens obtained during a primiparous full-term pregnancy and the subsequent occurrence of breast cancer in the mother. Nordic countries provide a unique setting for such a study because of the availability of large, centralized maternity cohorts and the access to a network of high quality nationwide databases, including cancer, population and birth registries, through which most of the information needed to carry out the proposed study will be obtained. Specific aims are the following: 1) To extend our preliminary observations on the protective role of first-trimester chronic gonadotropin (hCG). We hypothesize that the protection of hCG is maximal when the pregnancy occurs at young age and that the protection decreases with increasing age at pregnancy. Three groups of cases and controls will be studied defined on age at the pregnancy blood donation: <25 years, 25-29 years and 30-39 years 2) To determine whether or not associations similar to those hypothesized for hCG also apply to steroid hormones, as the experimental literature suggests. We will measure estradiol, progesterone, testosterone, and sex-hormone binding globulin (SHBG). With the proposed study we seek to cast light into the biological basis of the lifetime protection from breast cancer of a first full-term pregnancy experienced at young age-one of the best known protective associations in breast cancer epidemiology. A better understanding of such a protection will expand our comprehension of breast cancer and may open up new possibilities to devise and test novel preventive strategies, including chemoprevention, based on the ability to mimic the protective effect of pregnancy.

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Publications

Early Pregnancy Sex Steroids And Maternal Breast Cancer: A Nested Case-control Study
Authors: Fortner R.T. , Schock H. , Kaaks R. , Lehtinen M. , Pukkala E. , Lakso H.. , Tanner M. , Kallio R. , Joensuu H. , Grankvist K. , et al. .
Source: Cancer Research, 2014-12-01 00:00:00.0; 74(23), p. 6958-67.
PMID: 25281720
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Free -human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin And Maternal Risk Of Breast Cancer
Authors: Toriola A.T. , Tolockiene E. , Schock H. , Surcel H.M. , Zeleniuch-Jacquotte A. , Wadell G. , Toniolo P. , Lundin E. , Grankvist K. , Lukanova A. .
Source: Future Oncology (london, England), 2014 Feb; 10(3), p. 377-84.
PMID: 24559445
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Circulating Estrogens And Progesterone During Primiparous Pregnancies And Risk Of Maternal Breast Cancer
Authors: Lukanova A. , Surcel H.M. , Lundin E. , Kaasila M. , Lakso H.A. , Schock H. , Husing A. , Kaaks R. , Koskela P. , Grankvist K. , et al. .
Source: International Journal Of Cancer, 2012-02-15 00:00:00.0; 130(4), p. 910-20.
PMID: 21413009
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Circulating Insulin-like Growth Factor-i In Pregnancy And Maternal Risk Of Breast Cancer
Authors: Toriola A.T. , Lundin E. , Schock H. , Grankvist K. , Pukkala E. , Chen T. , Zeleniuch-Jacquotte A. , Toniolo P. , Lehtinen M. , Surcel H.M. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2011 Aug; 20(8), p. 1798-801.
PMID: 21680537
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Human Chorionic Gonadotropin In Pregnancy And Maternal Risk Of Breast Cancer
Authors: Toniolo P. , Grankvist K. , Wulff M. , Chen T. , Johansson R. , Schock H. , Lenner P. , Hallmans G. , Lehtinen M. , Kaaks R. , et al. .
Source: Cancer Research, 2010-09-01 00:00:00.0; 70(17), p. 6779-86.
PMID: 20713523
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Igf-i During Primiparous Pregnancy And Maternal Risk Of Breast Cancer
Authors: Chen T. , Lukanova A. , Grankvist K. , Zeleniuch-Jacquotte A. , Wulff M. , Johansson R. , Schock H. , Lenner P. , Hallmans G. , Wadell G. , et al. .
Source: Breast Cancer Research And Treatment, 2010 May; 121(1), p. 169-75.
PMID: 19728079
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Maternal Hormones During Early Pregnancy: A Cross-sectional Study
Authors: Chen T. , Lundin E. , Grankvist K. , Zeleniuch-Jacquotte A. , Wulff M. , Afanasyeva Y. , Schock H. , Johansson R. , Lenner P. , Hallmans G. , et al. .
Source: Cancer Causes & Control : Ccc, 2010 May; 21(5), p. 719-27.
PMID: 20084544
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Human Chorionic Gonadotropin And Alpha-fetoprotein Concentrations In Pregnancy And Maternal Risk Of Breast Cancer: A Nested Case-control Study
Authors: Lukanova A. , Andersson R. , Wulff M. , Zeleniuch-Jacquotte A. , Grankvist K. , Dossus L. , Afanasyeva Y. , Johansson R. , Arslan A.A. , Lenner P. , et al. .
Source: American Journal Of Epidemiology, 2008-12-01 00:00:00.0; 168(11), p. 1284-91.
PMID: 18936438
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Effect Of Long-term Storage On Hormone Measurements In Samples From Pregnant Women: The Experience Of The Finnish Maternity Cohort
Authors: Holl K. , Lundin E. , Kaasila M. , Grankvist K. , Afanasyeva Y. , Hallmans G. , Lehtinen M. , Pukkala E. , Surcel H.M. , Toniolo P. , et al. .
Source: Acta Oncologica (stockholm, Sweden), 2008; 47(3), p. 406-12.
PMID: 17891670
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