Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk

David M Euhus; Dawei Bu; Raheela Ashfaq; Xian-Jin Xie; Aihua Bian; A Marilyn Leitch; Cheryl M Lewis

doi:10.1158/1055-9965.EPI-06-1034

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Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk

Journal article

Peer reviewed

Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk

David M Euhus, Dawei Bu, Raheela Ashfaq, Xian-Jin Xie, Aihua Bian, A Marilyn Leitch and Cheryl M Lewis

Cancer epidemiology, biomarkers & prevention, Vol.16(9), pp.1812-1821

09/2007

DOI: 10.1158/1055-9965.EPI-06-1034

PMID: 17855699

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Abstract

Tumor suppressor gene (TSG) methylation is identified more frequently in random periareolar fine needle aspiration samples from women at high risk for breast cancer than women at lower risk. It is not known whether TSG methylation or atypia in nipple duct lavage (NDL) samples is related to predicted breast cancer risk. 514 NDL samples obtained from 150 women selected to represent a wide range of breast cancer risk were evaluated cytologically and by quantitative multiplex methylation-specific PCR for methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-beta2. Based on methylation patterns and cytology, NDL retrieved cancer cells from only 9% of breasts ipsilateral to a breast cancer. Methylation of >/=2 genes correlated with marked atypia by univariate analysis, but not multivariate analysis, that adjusted for sample cellularity and risk group classification. Both marked atypia and TSG methylation independently predicted abundant cellularity in multivariate analyses. Discrimination between Gail lower-risk ducts and Gail high-risk ducts was similar for marked atypia [odds ratio (OR), 3.48; P = 0.06] and measures of TSG methylation (OR, 3.51; P = 0.03). However, marked atypia provided better discrimination between Gail lower-risk ducts and ducts contralateral to a breast cancer (OR, 6.91; P = 0.003, compared with methylation OR, 4.21; P = 0.02). TSG methylation in NDL samples does not predict marked atypia after correcting for sample cellularity and risk group classification. Rather, both methylation and marked atypia are independently associated with highly cellular samples, Gail model risk classifications, and a personal history of breast cancer. This suggests the existence of related, but independent, pathogenic pathways in breast epithelium.

Predictive Value of Tests

Prognosis

Humans

Middle Aged

Breast Neoplasms - etiology

Cyclins - genetics

Risk

Nipples

Receptors, Retinoic Acid - genetics

Cyclin D2

Genes, APC

DNA Methylation

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Tumor Suppressor Proteins - genetics

Aged, 80 and over

Adult

Female

Aged

Body Fluids

Cytokines - genetics

Genes, Tumor Suppressor

Therapeutic Irrigation

Details

Title: Subtitle: Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk
Creators: David M Euhus - E6.222, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9155, USA. david.euhus@utsouthwestern.edu
Dawei Bu
Raheela Ashfaq
Xian-Jin Xie
Aihua Bian
A Marilyn Leitch
Cheryl M Lewis
Resource Type: Journal article
Publication Details: Cancer epidemiology, biomarkers & prevention, Vol.16(9), pp.1812-1821
DOI: 10.1158/1055-9965.EPI-06-1034
PMID: 17855699
NLM abbreviation: Cancer Epidemiol Biomarkers Prev
ISSN: 1055-9965
eISSN: 1538-7755
Publisher: United States
Language: English
Date published: 09/2007
Academic Unit: Preventive and Community Dentistry; Biostatistics; Dental Research
Record Identifier: 9983917793202771

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