Copy number variation at 6q13 functions as a long-range regulator and is associated with pancreatic cancer risk.
Copy number variations (CNVs) have been recognized to contribute to phenotypic variations and to be associated with susceptibility to certain complex diseases. This study examined the functional significance of CNVR2966.1 at 6q13 and its association with pancreatic cancer susceptibility. The CNVR2966.1 was found to be a 10,379 bp nucleotides deletion/insertion within the uniform boundaries chromosome 6: 74 648 791-74 659 169. Luciferase reporter gene assays revealed an active regulator in CNVR2966.1, which was demonstrated by circular chromosome conformation capture assays to physically interact with the upstream functional sequence of CDKN2B. CDKN2B transcription levels in pancreatic tissues were therefore significantly higher in individuals with two copies of CNVR2966.1 than in those with low copy number of CNVR2966.1. The risk of pancreatic cancer observed in 1027 cases and 1031 controls was significantly associated with copy number of CNVR2966.1, with the odds ratio being 1.31 (95% confidence interval = 1.08-1.60; P = 0.007) for one copy genotype compared with two copies genotype. These results suggest that CNVR2966.1 is associated with pancreatic cancer risk probably owing to its effect on long-range regulation of CDKN2B.
State Key Laboratory of Molecular Oncology and Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Liming
L
Huang
Dianke
D
Yu
Chen
C
Wu
Kan
K
Zhai
Guoliang
G
Jiang
Guangwen
G
Cao
Chunyou
C
Wang
Yu
Y
Liu
Menghong
M
Sun
Zhaoshen
Z
Li
Wen
W
Tan
Dongxin
D
Lin
D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D056915:DNA Copy Number Variations; D005809:Genes, Regulator; D020022:Genetic Predisposition to Disease; D006801:Humans; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15