Multiple gene-specific DNA methylation in blood leukocytes and colorectal cancer risk: a case-control study in China
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Yupeng Liu1, Yibaina Wang1, Fulan Hu1, Hongru Sun1, Zuoming Zhang1, Xuan Wang1, Xiang Luo1, Lin Zhu1, Rong Huang1, Yan Li1, Guangxiao Li1, Xia Li1, Shangqun Lin1, Fan Wang1, Yanhong Liu2, Jiesheng Rong3, Huiping Yuan4 and Yashuang Zhao1
1Department of Epidemiology, Public Health College, Harbin Medical University, Harbin 150081, Heilongjiang Province, The People’s Republic of China
2Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, The People’s Republic of China
3Department of Orthopedics Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, The People’s Republic of China
4Key Laboratory of Ophthalmology, Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, The People’s Republic of China
Yashuang Zhao, email: firstname.lastname@example.org
Keywords: colorectal cancer risk, DNA methylation, leukocytes
Received: February 03, 2017 Accepted: April 07, 2017 Published: May 22, 2017
The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.
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