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Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer
  1. Hsien-Feng Chang1,
  2. Chang-Chieh Wu2,
  3. Chien-An Sun3,
  4. Chi-Ming Chu1,
  5. Fu-Gong Lin1,
  6. Jih-Fu Hsieh1,
  7. Chih-Hsiung Hsu4,
  8. Chi-Hua Huang1,
  9. Tsan Yang5,
  10. Yang-Ming Tsai1,
  11. Jen-Chun Kuan6,
  12. Yu-Ching Chou1
  1. 1School of Public Health, National Defense Medical Center, Taipei, Taiwan
  2. 2Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  3. 3Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
  4. 4Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
  5. 5Department of Health Business Administration, Meiho University, Pingtung, Taiwan
  6. 6Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
  1. Correspondence to Dr Yu-Ching Chou, School of Public Health, National Defense Medical Center, No.161 Sec. 6, Minquan E. Rd., Neihu Dist, Taipei 11490, Taiwan; trishow{at}mail.ndmctsgh.edu.tw

Abstract

Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p<0.001). In addition, after stratification by promoter methylation in 3 combined genes in the matched normal tissues, we observed a joint effect after adjusting for sex, age at surgery, and adjuvant chemotherapy, yielding a significant OR of 20.35 (95% CI 4.16 to 99.57; p<0.001). DNA methylation status would significantly increase the recurrence risk of CRC with a significant impact on joint effect between DNA methylation and clinical stage, particularly in matched normal tissues. This was attributed to molecular changes that could not be examined on the basis of clinical pathology. Our interaction results may serve as a reference marker for evaluating the risk of recurrence in future studies.

  • Colon
  • Recurrence
  • Cancer

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