Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 134, Issue 3, Pages 1103-1114Publisher
SPRINGER
DOI: 10.1007/s10549-012-2038-0
Keywords
Age; Breast cancer; LINE-1; Methylation; Prognosis
Categories
Funding
- Susan G. Komen Breast Cancer Foundation [BCTR0707528]
- Susan Gonda (Goldschmied) Foundation (DSBH, Los Angeles, CA)
- Ruth and Martin H. Weil Fund (DSBH, Los Angeles, CA)
- Associates for Breast and Prostate Cancer (ABC) Studies
- Fashion Footwear Association of New York (FFANY)
- California Breast Cancer Research Program [16IB-0076]
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Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence, methylation status can influence tumor progression. In this study, the clinical significance of LINE-1 methylation status was assessed in primary breast cancer in young versus old breast cancer patients. LINE-1 methylation index (MI) was assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR assay. Initially, LINE-1 MI was assessed in a preliminary study of 235 tissues representing different stages of ductal breast cancer development. Next, an independent cohort of 379 primary ductal breast cancer patients (median follow-up 18.9 years) was studied. LINE-1 hypomethylation was shown to occur in DCIS and invasive breast cancer. In primary breast cancer it was associated with pathological tumor stage (p = 0.026), lymph node metastasis (p = 0.022), and higher age at diagnosis (> 55, p < 0.001). In multivariate analysis, LINE-1 hypomethylation was associated with decreased OS (HR 2.19, 95 % CI 1.17-4.09, log-rank p = 0.014), DFS (HR 2.05, 95 % CI 1.14-3.67, log-rank p = 0.016) and increased DR (HR 2.83, 95 % CI 1.53-5.21, log-rank p = 0.001) in younger (a parts per thousand currency sign55 years), but not older patients (> 55 years). LINE-1 analysis of primary breast cancer demonstrated cancer-related age-dependent hypomethylation. In patients a parts per thousand currency sign55 years, LINE-1 hypomethylation portends a high-risk of DR.
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