Increased breast tissue receptor activator of nuclear factor- κB ligand (RANKL) gene expression is associated with higher mammographic density in premenopausal women
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Adetunji T. Toriola1, Ha X. Dang2, Ian S. Hagemann3, Catherine M. Appleton4, Graham A. Colditz1, Jingqin Luo1 and Christopher A. Maher2
1Department of Surgery, Division of Public Health Sciences, and Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
2The McDonnell Genome Institute, and Department of Medicine, Washington University, St. Louis, MO, USA
3Genomics and Pathology Services, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
4Division of Diagnostic Radiology, Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
Adetunji T. Toriola, email: [email protected]
Keywords: mammographic density, breast cancer, RANKL, premenopausal women, prevention
Received: April 12, 2017 Accepted: May 01, 2017 Published: May 17, 2017
Increased mammographic breast density is associated with a 4–6-fold increased risk of breast cancer, yet lifestyle factors that can reduce dense breasts are yet to be identified, and viable prevention strategies to reduce breast density-associated breast cancer development are yet to be developed. We investigated the associations of breast tissue receptor activator of nuclear factor-κB (RANK) pathway gene expression with mammographic density in 48 premenopausal women, with no previous history of cancer. Gene expression levels were measured in total RNA isolated from formalin-fixed paraffin-embedded breast tissue samples, using the NanoString nCounter platform. Mammographic density was classified based on the American College of Radiology Breast Imaging Reporting and Data (BI-RADS). Linear regression was used to evaluate associations between gene expression and mammographic density. The mean age of participants was 44.4 years. Women with higher breast tissue RANKL (TNFSF11) (p-value = 0.0076), and TNF (p-value = 0.007) gene expression had higher mammographic density. Our finding provides mechanistic support for a breast cancer chemoprevention trial with a RANKL inhibitor among high-risk premenopausal women with dense breasts.
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