Genome-wide expression profiling-based copy number variations and colorectal cancer risk in Chinese.

Genetic factors play important roles in colorectal carcinogenesis. This study was aimed to evaluate the effects of gene expression-related copy number variations (CNVs) on the risk of colorectal cancer in Chinese. Expression Quantitative Trait Locus (eQTL) mapping was conducted to explore the most regulatable gene expressions by CNVs among the whole genome based on publicly available data. Then a case-control study was performed to evaluate the associations between copy numbers of the most regulatable genes and colorectal cancer. The influence of the target CNVs on the expression of corresponding gene and protein was verified in colorectal tissue, and the biological effects of these CNVs on cell-cycle arrest and apoptosis of colon cancer cell lines were further detected. The eQTL revealed the most significant association between CNV of HM3_CNP_342 and gene expressions of human leukocyte antigen (HLA)-DQA1 and HLA-DQB1 among the whole genome. The later case-control study found that amplified HLA-DQB1 was inversely associated with colorectal cancer risk (odds ratio = 0.73; 95% confidence interval: 0.58-0.93), especially among those with a family history of cancer. The positive association between amplified HLA-DQB1 and upregulation of gene and protein was validated in colorectal tissue. In addition, overexpression of HLA-DQB1 in dendritic cells promoted cell-cycle arrest and apoptosis of cocultured SW480 and HCT116 cell lines, and vice versa. Our study suggests that the amplified copy number of HLA-DQB1 is associated with lower risk of colorectal cancer and able to induce the apoptosis of colon cancer cells, which implies the potential of HLA class II in cancer predisposition and immunotherapy.