Cancer of the breast is the most common major cancer among women in the United States, and the incidence rate of female breast cancer has been increasing in the United States and in many other areas of the world. In Connecticut, the incidence rate of female breast cancer has been increasing during the past several decades, particularly in women age 50 and over. While considerable efforts have been made, little is known about the etiology of breast cancer and the factors which might be responsible for the observed time trends. Recent epidemiologic studies strongly suggest that environmental exposure to organochlorine residues increases the risk of female breast cancer. This association is biologically plausible. Many organochlorine compounds are known animal carcinogens, suspected human carcinogens, have tumor promotion activity, possess estrogenic activity, and may compromise immune function. Due to the inconclusive nature of the recent epidemiologic studies (small numbers of subjects, lack of control for all potential confounders) and the widespread exposure to organochlorine compounds, there exists an urgent need for more rigorous epidemiologic studies. Against this background, a case-control study of organochlorine compound exposure and risk of breast cancer in Connecticut is proposed. More specifically, this study will test the hypotheses that a) exposure to total polychlorinated biphenyls (PCBs) and specific major PCB congeners increases the risk of female breast cancer; b) exposure to DDT and its most stable and persistent metabolite DDE increases the risk of female breast cancer; and c) exposure to benzene hexachloride (BHC) isomers, particularly alpha-, beta- and gamma-BHC, increases the risk of female breast cancer. Cases and controls will be patients diagnosed over a three and one-quarter year period at the Yale- New Haven Hospital. The case group will consist of 200 incident primary breast cancer patients with in situ or stage I-III disease. An equal number of controls will be selected from women who are diagnosed with benign breast disease (excluding atypical hyperplasia). Cases and controls will be between ages 50 and 79 and will have sufficient non-diagnostic breast adipose tissue for chemical analysis. The concentration of organochlorine compounds in breast adipose tissue will be analyzed by gas chromatography and compared between the cases and controls. Subsequent to tissue collection, cases and controls will be interviewed in their homes by trained interviewers using a standardized, structured questionnaire to obtain information regarding potential confounding factors, including age, lactation history, body mass index, dietary intakes, exposure to non- organochlorine pesticides, and reproductive history. Statistical analyses will be performed using standard multivariable techniques to address the study hypotheses and to control for confounding.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA062986-03S1
Application #
2104533
Study Section
Special Emphasis Panel (SRC (94))
Project Start
1993-09-30
Project End
1997-09-29
Budget Start
1995-09-30
Budget End
1996-09-29
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Li, Qian; Holford, Theodore R; Zhang, Yawei et al. (2013) Dietary fiber intake and risk of breast cancer by menopausal and estrogen receptor status. Eur J Nutr 52:217-23
Li, Qian; Zheng, Tongzhang; Holford, Theodore R et al. (2010) Light at night and breast cancer risk: results from a population-based case-control study in Connecticut, USA. Cancer Causes Control 21:2281-5
Zhu, Yong; Stevens, Richard G; Leaderer, Derek et al. (2008) Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk. Breast Cancer Res Treat 107:421-5
Zhu, Yong; Zheng, Tongzhang; Stevens, Richard G et al. (2006) Does ""clock"" matter in prostate cancer? Cancer Epidemiol Biomarkers Prev 15:3-5
Zhu, Yong; Brown, Heather N; Zhang, Yawei et al. (2005) Period3 structural variation: a circadian biomarker associated with breast cancer in young women. Cancer Epidemiol Biomarkers Prev 14:268-70
Zhu, Yong; Brown, Heather N; Zhang, Yawei et al. (2005) Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status. Breast Cancer Res 7:R745-52
Goodstine, Shelley L; Zheng, Tongzhang; Holford, Theodore R et al. (2003) Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women. J Nutr 133:1409-14
Zheng, T; Holford, T R; Mayne, S T et al. (2002) Radiation exposure from diagnostic and therapeutic treatments and risk of breast cancer. Eur J Cancer Prev 11:229-35
Zheng, Tongzhang; Holford, Theodore R; Zahm, Shelia H et al. (2002) Cigarette smoking, glutathione-s-transferase M1 and t1 genetic polymorphisms, and breast cancer risk (United States). Cancer Causes Control 13:637-45
Zheng, T; Holford, T R; Taylor Mayne, S et al. (2002) A case-control study of occupation and breast-cancer risk in Connecticut. J Cancer Epidemiol Prev 7:3-11

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