Original Article
Copyright ©2012 Baishideng. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2012; 4(8): 193-201
Published online Aug 15, 2012. doi: 10.4251/wjgo.v4.i8.193
Leukocyte DNA methylation and colorectal cancer among male smokers
Ying Gao, Keith Killian, Hong Zhang, Kai Yu, Qi-Zhai Li, Stephanie Weinstein, Jarmo Virtamo, Margaret Tucker, Philip Taylor, Demetrius Albanes, Paul Meltzer, Neil Caporaso
Ying Gao, Kai Yu, Stephanie Weinstein, Margaret Tucker, Philip Taylor, Demetrius Albanes, Neil Caporaso, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, United States
Keith Killian, Paul Meltzer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, United States
Hong Zhang, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai 200433, China
Qi-Zhai Li, Department of Statistics, Chinese Academy of Sciences, Beijing 100190, China
Jarmo Virtamo, National Public Health Institute, Helsinki FI-00271, Finland
Author contributions: Gao Y and Caporaso N designed the study; Gao Y, Zhang H, Yu K and Li QZ analyzed the data; Gao Y and Caporaso N wrote the report; Killian K and Meltzer P conducted laboratory assays; all authors read, gave comments, and approved the final version of the manuscript; Gao Y had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Supported by Grants from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
Correspondence to: Ying Gao, MD, PhD, Professor, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Bldg. EPS/Room 7110, NIH/NCI, Bethesda, MD 20892, United States. gaoying@mail.nih.gov
Telephone: +1-301-4969249 Fax: +1-301-4024489
Received: January 13, 2012
Revised: July 13, 2012
Accepted: July 20, 2012
Published online: August 15, 2012

AIM: To explore the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the α-tocopherol, β-carotene cancer prevention study.

METHODS: About 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression.

RESULTS: We found that methylation changes of 31 CpG sites were associated with CRC risk at P < 0.01 level. Though none of these 31 sites remained statistically significant after Bonferroni correction, the most statistically significant CpG site associated with CRC risk achieved a P value of 1.0 × 10-4. The CpG site is located in DSP gene, and the risk estimate was 1.52 (95% CI: 0.91-2.53) and 2.62 (95% CI: 1.65-4.17) for the second and third tertile comparing with the lowest tertile respectively. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression.

CONCLUSION: The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.

Keywords: DNA methylation, Colorectal cancer, Susceptibility