@article{5e2adcbcb7a448a9888145af25161c82,
title = "Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy",
abstract = "Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.",
keywords = "Breast diseases, Breast neoplasms, Breast pathology, Hyperplasia, Mammographic density, Telomere",
author = "Clara Bodelon and Heaphy, {Christopher M.} and Meeker, {Alan K.} and Berta Geller and Vacek, {Pamela M.} and Weaver, {Donald L.} and Chicoine, {Rachael E.} and Shepherd, {John A.} and Mahmoudzadeh, {Amir Pasha} and Patel, {Deesha A.} and Brinton, {Louise A.} and Sherman, {Mark E.} and Gierach, {Gretchen L.}",
note = "Funding Information: This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute and National Cancer Institute federal funds awarded under Contract No. HHSN261200800001E to SAIC-Frederick, Inc. Breast Cancer Research Stamp Funds and cooperative agreement U01CA70013 (B. Geller, P. Vacek, D. Weaver, R. Chicoine) and 1R21CA157254 (J. Shepherd, A. Mahmoudzadeh) from the National Cancer Institute funded some of the data collection and image analysis for this study. Grant number M01 RR000109 from the National Center for Research Resources funded the blood processing at the University of Vermont{\textquoteright}s General Clinical Research Center. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors are indebted to the participants in the BREAST Stamp Project for their outstanding cooperation and to the physicians, pathologists, nurses, technologists, and interviewers for their efforts in the field. The authors thank Clair Bove, Patricia Lutton, Ellen Young, Aileen Burke, Laura Linville, Daphne Papathomas, and Jeff Wang for research assistance. We also thank Bo Fan from the University of California at San Francisco for providing the area measures of mammographic density, Bharathi Anekella from SeraCare Life Sciences for assistance with DNA extraction, Sally Larson from the Cancer Genomics Research Laboratory for assistance with DNA quantitation, Janet Lawler-Heaver and Kerry Grace Morrissey from Westat for study management support, and Franklin Demuth at Information Management Services for data support and analysis. Publisher Copyright: {\textcopyright} 2015 Bodelon et al.",
year = "2015",
month = oct,
day = "30",
doi = "10.1186/s12885-015-1860-2",
language = "English (US)",
volume = "15",
journal = "BMC cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",
}