Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling.
BACKGROUND
Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer.


RESULTS
A 41-miRNA model distinguished breast cancer risk in the discovery study (accuracy of 83.3%), which was replicated in the independent study (accuracy = 63.4%, P=0.09). Among the 41 miRNA, 20 miRNAs were detectable in serum, and predicted breast cancer occurrence within 18 months of blood draw (accuracy 53%, P=0.06). These risk-related miRNAs were enriched for HER-2 and estrogen-dependent breast cancer signaling.


METHODS
MiRNAs were assessed in two cross-sectional studies of women without breast cancer and a nested case-control study of breast cancer. Using breast tissues, a multivariate analysis was used to model women with high and low breast cancer risk (based upon Gail risk model) in a discovery study of women without breast cancer (n=90), and applied to an independent replication study (n=71). The model was then assessed using serum samples from the nested case-control study (n=410).


CONCLUSIONS
Studying breast tissues of women without breast cancer revealed miRNAs correlated with breast cancer risk, which were then found to be altered in the serum of women who later developed breast cancer. These results serve as proof-of-principle that miRNAs in women without breast cancer may be useful for predicting breast cancer risk and/or as an adjunct for breast cancer early detection. The miRNAs identified herein may be involved in breast carcinogenic pathways because they were first identified in the breast tissues of healthy women.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Cenny
C
Taslim
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Daniel Y
DY
Weng
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Theodore M
TM
Brasky
Distilled Spirits Council of the United States, Washington, DC, USA.
Ramona G
RG
Dumitrescu
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Kun
K
Huang
Department of Pathology, Georgetown University, Washington, DC, USA.
Bhaskar V S
BV
Kallakury
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Shiva
S
Krishnan
Department of Epidemiology, Rutgers University, New Brunswick, NJ, USA.
Adana A
AA
Llanos
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
Catalin
C
Marian
Center for Biostatistics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Joseph
J
McElroy
Pioneer Valley Life Sciences Institute, Springfield, MA, USA.
Sallie S
SS
Schneider
Department of Plastic Surgery, Georgetown University Hospital, Washington, DC, USA.
Scott L
SL
Spear
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Melissa A
MA
Troester
Departement of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
Jo L
JL
Freudenheim
Health Informatics Institute, University of South Florida, Tampa, FL, USA.
Susan
S
Geyer
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Peter G
PG
Shields
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D012306:Risk
D035683:MicroRNAs
breast cancer risk prediction; epigenetics; healthy women; microRNA; tissue-based biomarkers