International Journal of Colorectal Disease

, Volume 28, Issue 1, pp 139–147 | Cite as

Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer

  • Seung-Chul Pack
  • Hye-Ran Kim
  • Sang-Woo Lim
  • Hwan-Young Kim
  • Jung-Yun Ko
  • Ki-Sang Lee
  • David Hwang
  • Seong-Il Park
  • Hoon Kang
  • Sang-Wook Park
  • Gun-Young Hong
  • Se-Min Hwang
  • Myung-Geun ShinEmail author
  • Soong LeeEmail author
Original Article



The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.


The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn’s disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis.


This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR = 6.67, 95 % CI = 1.19–23.4, P = 0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60–80 %) in our limited number of colorectal cancer patients.


Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC.


Colorectal cancer methylation APC E-cadherin SMAD4 FHIT DAPK1 



This work was supported by the Seonam University Namgwang Hospital and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (No.2010-0024326) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0015304).


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Seung-Chul Pack
    • 1
  • Hye-Ran Kim
    • 5
  • Sang-Woo Lim
    • 2
  • Hwan-Young Kim
    • 4
  • Jung-Yun Ko
    • 4
  • Ki-Sang Lee
    • 1
  • David Hwang
    • 1
  • Seong-Il Park
    • 1
  • Hoon Kang
    • 1
  • Sang-Wook Park
    • 3
  • Gun-Young Hong
    • 3
  • Se-Min Hwang
    • 6
  • Myung-Geun Shin
    • 4
    • 7
    Email author
  • Soong Lee
    • 1
    Email author
  1. 1.Department of Internal MedicineSeonam University Namgwang HospitalGwang-juSouth Korea
  2. 2.Department of Colon and Rectal SurgeryChonnam National University Hwasun HospitalHwasunSouth Korea
  3. 3.Department of Internal MedicineKwangju Christian HospitalGwang-juSouth Korea
  4. 4.Department of Laboratory Medicine and Mitochondrial Research LaboratoryChonnam National University Hwasun HospitalHwasunSouth Korea
  5. 5.Brain Korea 21 Project, Center for Biomedical Human ResourcesChonnam National UniversityGwangjuSouth Korea
  6. 6.Department of Preventive Medicinethe Armed Forces CommandSeoulSouth Korea
  7. 7.Department of Laboratory MedicineHwasun-gunSouth Korea

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