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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Acknowledgment

Supported in part by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (Grant 23689061).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

    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

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  1. Hironobu Shigaki MD
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  2. Yoshifumi Baba MD, PhD
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  3. Masayuki Watanabe MD, PhD
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  4. Shiro Iwagami MD
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  5. Keisuke Miyake MSc
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  6. Takatsugu Ishimoto MD, PhD
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  7. Masaaki Iwatsuki MD, PhD
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  8. Hideo Baba MD, PhD
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Correspondence to Hideo Baba MD, PhD.

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Shigaki, H., Baba, Y., Watanabe, M. et al. LINE-1 Hypomethylation in Noncancerous Esophageal Mucosae is Associated with Smoking History. Ann Surg Oncol 19, 4238–4243 (2012). https://doi.org/10.1245/s10434-012-2488-y

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  • DOI: https://doi.org/10.1245/s10434-012-2488-y

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