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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2012

01-12-2012 | Gastrointestinal Oncology

LINE-1 Hypomethylation in Noncancerous Esophageal Mucosae is Associated with Smoking History

Authors: Hironobu Shigaki, MD, Yoshifumi Baba, MD, PhD, Masayuki Watanabe, MD, PhD, Shiro Iwagami, MD, Keisuke Miyake, MSc, Takatsugu Ishimoto, MD, PhD, Masaaki Iwatsuki, MD, PhD, Hideo Baba, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2012

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ABSTRACT

Background

Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Selected gene promoter hypermethylation in normal esophageal mucosae has attracted attention as a surrogate marker for the epigenetic field defect induced by smoking and/or drinking in esophageal squamous cell carcinoma (ESCC). However, the significance of global DNA hypomethylation for field cancerization remains unclear.

Methods

By using histologically normal esophageal mucosa samples from 109 ESCC cases and 20 autopsy cases without ESCCs, we measured long interspersed nucleotide element 1 (LINE-1) methylation levels by pyrosequencing, which correlates with global DNA methylation level.

Results

LINE-1 methylation levels in normal esophageal mucosae of ESCC patients were significantly lower than those of autopsy individuals (P = 0.017). LINE-1 methylation of noncancerous mucosae ranged 68.3–93.0 on a 0–100 scale (mean 81.7, median 82.2, standard deviation 5.9). LINE-1 hypomethylation was significantly associated with smoking history (P = 0.014 for smoking duration; P = 0.0017 for number of cigarettes per day; P = 0.0002 for tobacco pack-year). LINE-1 methylation was not associated with alcohol drinking or age at diagnosis.

Conclusions

A history of tobacco use was significantly associated with LINE-1 hypomethylation in noncancerous esophageal mucosae of ESCC patients. These results support the potential of LINE-1 methylation level as an indicator of epigenetic field for ESCC cancerization, particularly when caused by tobacco smoking.
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Metadata
Title
LINE-1 Hypomethylation in Noncancerous Esophageal Mucosae is Associated with Smoking History
Authors
Hironobu Shigaki, MD
Yoshifumi Baba, MD, PhD
Masayuki Watanabe, MD, PhD
Shiro Iwagami, MD
Keisuke Miyake, MSc
Takatsugu Ishimoto, MD, PhD
Masaaki Iwatsuki, MD, PhD
Hideo Baba, MD, PhD
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 13/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2488-y

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