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Association of copy number variation in ethanol metabolic pathway genes with susceptibility of colorectal cancer



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Association of copy number variation in ethanol metabolic pathway genes with susceptibility of colorectal cancer


LONG Qi CHEN Weiyan WANG Lingqiao LI Rong XIANG Menglong YANG Huan CAO Jia ZHOU Ziyuan

Department of Environment Health, Institute of Toxicology, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038; Medical Company of Troop 77120, Chengdu, Sichuan Province, 610081, China


colorectal cancer ADH1B ALDH2 CYP2E1 copy number variation

R195.4; R394.5; R735.3

Objective    To investigate the relationship of the copy number variation (CNV) of 3 metabolic pathway genes for ethanol, alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) with the susceptibility of colorectal cancer (CRC) in the population living in the Southwest China. Methods    A total of 449 CRC patients and 449 cancer-free controls were recruited during 2001 and 2004 from the 3 affiliated hospital of Army Medical University. The copy number of the 3 candidate genes were tested with a multiplex gene copy number quantitation method AccuCopyTM. Then 10% samples were further verified for the copy number. Unconditional logistic regression analysis was applied to evaluate the association between germline CNV genotypes and CRC risk. Results    There was no significant difference in the gene copy number of both ADH1B and ALDH2 between CRC patients and normal controls, and the number was 2 copies. While the copy number of CYP2E1 had significantly different distribution between the CRC patients and control subjects (P=0.046). Moreover, logistic regression analysis showed that the gain of CYP2E1 was a risk factor for CRC (OR=2.47, 95%CI: 1.04~5.85,P=0.041). A further assessment for possible modifications of surrounding factors in a stratification analysis indicated that a positive association of CYP2E1 gain and CRC risk was found in subpopulations of older than 50 years, colon cancer, and daily ethanol consumption ≤50 g. Conclusion    The gain of CYP2E1 copy number is associated with CRC in the population in the Southwest China.


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Last Update: 2018-06-14