Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer.
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.
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Hsien-Feng
HF
Chang
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Chang-Chieh
CC
Wu
Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
Chien-An
CA
Sun
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Chi-Ming
CM
Chu
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Fu-Gong
FG
Lin
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Jih-Fu
JF
Hsieh
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Chih-Hsiung
CH
Hsu
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Chi-Hua
CH
Huang
Department of Health Business Administration, Meiho University, Pingtung, Taiwan.
Tsan
T
Yang
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Yang-Ming
YM
Tsai
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Jen-Chun
JC
Kuan
School of Public Health, National Defense Medical Center, Taipei, Taiwan.
Yu-Ching
YC
Chou
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality*; D009367:Neoplasm Staging; D016017:Odds Ratio; D011401:Promoter Regions, Genetic; D012307:Risk Factors
Cancer; Colon; Recurrence