Abstract Background: The DNA methylation alterations that occur in human cancers include global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Global DNA hypomethylation plays an important role in genomic instability, leading to cancer development. Since LINE-1 or the L1 retrotransposon constitutes a substantial portion of the human genome, LINE-1 methylation status reflects global DNA methylation. Our previous study has revealed that LINE-1 methylation level is a potential surrogate marker for epigenetic field defects induced by tobacco smoking in esophageal cancer patients. Given that liver fibrosis can be one phenomena of field cancerization theory in hepatocellular carcinoma (HCC), we examined the relationship between LINE-1 methylation level and fibrosis status in noncancerous liver tissues of HCC patients. Methods: Using histologically normal liver tissue samples and matched tumor tissue samples from 89 HCC cases, we measured LINE-1 methylation levels by pyrosequencing technology. Results: LINE-1 methylation of noncancerous liver tissues range was 35.8-97.3 of a 0-100 scale (mean: 78.1; median: 81.0; standard deviation: 11.9). HCC tissues showed significantly lower levels of LINE-1 methylation than matched normal tissue (P<0.01). LINE-1 methylation of noncancerous liver tissues was not associated with age, sex, Hepatitis B Virus infection, or Hepatitis C Virus infection. Interestingly, LINE-1 methylation level of noncancerous liver tissues with severe fibrosis (score 2-4) was significantly lower than that with mild fibrosis (score 0-1) (P=0.013). Conclusion: Liver fibrosis in noncancerous liver tissues of HCC patients was significantly associated with LINE-1 hypomethylation. This result supports the potential of LINE-1 methylation level as an indicator of epigenetic field for HCC cancerization. Citation Format: Yoshifumi Baba, Kazuto Harada, Keisuke Kosumi, Hiromitsu Hayashi, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba. The relationship between LINE-1 hypomethylation and fibrosis status in noncancerous liver tissues of hepatocellular carcinoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 408. doi:10.1158/1538-7445.AM2014-408