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Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study
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Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study
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Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study
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Journal Article
Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study
2012
Overview
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 (≤55 years), but not older patients (>55 years). LINE-1 analysis of primary breast cancer demonstrated cancer-related age-dependent hypomethylation. In patients ≤55 years, LINE-1 hypomethylation portends a high-risk of DR.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
/ Age
/ Analysis
/ Biological and medical sciences
/ Breast Neoplasms - diagnosis
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - mortality
/ Cancer
/ Cell Transformation, Neoplastic - genetics
/ Female
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Long Interspersed Nucleotide Elements
/ Medicine
/ Oncology
/ Tumors
