The objective of this study is to investigate gene-environment interactions in the etiology of breast cancer. We propose to establish a repository of epidemiologic risk factor information and biologic specimens from 900 women with asynchronous bilateral breast cancer and 2700 women with unilateral breast cancer who will be ascertained through 6 population-based tumor registries in the US and Denmark. All subjects will be interviewed using a structured questionnaire and blood samples will be collected for genetic analyses. Our initial plan for using this repository is to examine the interaction of radiation exposure, the ATM gene, and breast cancer. Ionizing radiation is known to be a breast carcinogen and recent studies suggest that the ATM gene may increase susceptibility to radiation-induced breast cancer. Our hypothesis is that women who are ATM gene carriers and who have received radiation therapy as part of breast conservation treatment, are at especially high risk of developing second primary contralateral breast cancer. We will also provide descriptive statistics on the prevalence of ATM in this large population-based sample of women. ATM heterozygosity will be assessed through an efficient staged approach appropriate for analysis of this complex gene. For subjects who received RT, radiation scatter dose to the contralateral breast will be reconstructed. The unique repository that we establish will be critical for future interdisciplinary investigations into the mechanisms and nature of gene-gene and gene-environment interaction influencing susceptibility to breast cancer. The study of second primaries presents a particularly promising context in which to disentangle the complex interactions among hormonal, genetic, and environmental factors influencing breast carcinogenesis as any important etiologic factors (e.g. genetic abnormalities) will be more prevalent among women who already have breast cancer than in the general population. Further, the rising incidence of breast cancer coupled with improved survival, has placed an increased number of women at risk for second primary breast cancer making it an issue of public health importance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA083178-01
Application #
2908946
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (M1))
Program Officer
Seminara, Daniela
Project Start
1999-09-30
Project End
2004-08-31
Budget Start
1999-09-30
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Knight, Julia A; Blackmore, Kristina M; Fan, Jing et al. (2018) The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study. Breast Cancer Res 20:23
Langballe, Rikke; John, Esther M; Malone, Kathleen E et al. (2018) Agreement between self-reported and register-based cardiovascular events among Danish breast cancer survivors. J Cancer Surviv 12:95-100
Reiner, Anne S; Sisti, Julia; John, Esther M et al. (2018) Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study. J Clin Oncol 36:1513-1520
Reiner, Anne S; Lynch, Charles F; Sisti, Julia S et al. (2017) Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population. Breast Cancer Res 19:83
Knight, Julia A; Fan, Jing; Malone, Kathleen E et al. (2017) Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study. Int J Cancer 141:916-924
Bernstein, Jonine L; WECARE Study Collaborative Group; Concannon, Patrick (2017) ATM, radiation, and the risk of second primary breast cancer. Int J Radiat Biol 93:1121-1127
Langballe, Rikke; Mellemkjær, Lene; Malone, Kathleen E et al. (2016) Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study. Breast Cancer Res 18:65
Brooks, Jennifer D; John, Esther M; Mellemkjaer, Lene et al. (2016) Body mass index, weight change, and risk of second primary breast cancer in the WECARE study: influence of estrogen receptor status of the first breast cancer. Cancer Med 5:3282-3291
Sisti, Julia S; Bernstein, Jonine L; Lynch, Charles F et al. (2015) Reproductive factors, tumor estrogen receptor status and contralateral breast cancer risk: results from the WECARE study. Springerplus 4:825
Rakovski, Cyril; Langholz, Bryan (2015) A post-hoc Unweighted Analysis of Counter-Matched Case-Control Data. Int J Biostat 11:223-32

Showing the most recent 10 out of 44 publications