Title | Genetic variation determines VEGF-A plasma levels in cancer patients. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Innocenti, Federico, Chen Jiang, Alexander B. Sibley, Amy S. Etheridge, Ace J. Hatch, Stefanie Denning, Donna Niedzwiecki, Ivo D. Shterev, Jiaxing Lin, Yoichi Furukawa, Michiaki Kubo, Hedy L. Kindler, Todd J Auman, Alan P. Venook, Herbert I. Hurwitz, Howard L. McLeod, Mark J. Ratain, Raluca Gordân, Andrew B. Nixon, and Kouros Owzar |
Journal | Sci Rep |
Volume | 8 |
Issue | 1 |
Pagination | 16332 |
Date Published | 2018 Nov 05 |
ISSN | 2045-2322 |
Keywords | Adult, Aged, Aged, 80 and over, Colorectal Neoplasms, Female, Humans, Male, Middle Aged, Neovascularization, Pathologic, NFATC Transcription Factors, Polymorphism, Single Nucleotide, RNA, Messenger, Vascular Endothelial Growth Factor A, Young Adult |
Abstract | Angiogenesis is essential in tumor biology and is regulated by vascular endothelial growth factor (VEGF) ligands and receptors. Here we aimed to discover genetic variants associated with levels of circulating angiogenic proteins in cancer patients. Plasma was collected at baseline in 216 pancreatic and 114 colorectal cancer patients. Thirty-one angiogenic proteins were measured by ELISA. 484,523 Single Nucleotide Polymorphisms (SNP) were tested for association with plasma levels for each protein in pancreatic cancer patients. Three top-ranked hits were then genotyped in colorectal cancer patients, where associations with the same proteins were measured. The results demonstrated rs2284284 and MCP1 (P-value = 6.7e-08), rs7504372 and VEGF-C (P-value = 9.8e-09), and rs7767396 and VEGF-A (P-value = 5.8e-09) were SNP-protein pairs identified in pancreatic cancer patients. In colorectal cancer patients, only rs7767396 (A > G) and VEGF-A was validated (P-value = 5.18e-05). The AA genotype of rs7767396 exhibited 2.04-2.3 and 2.7-3.4-fold higher VEGF-A levels than those with AG and GG genotypes. The G allele of rs7767396 reduces binding of the NF-AT1 transcription factor. In conclusion, a common genetic variant predicts the plasma levels of VEGF-A in cancer patients through altered binding of NF-AT1. |
DOI | 10.1038/s41598-018-34506-4 |
Alternate Journal | Sci Rep |
Original Publication | Genetic variation determines VEGF-A plasma levels in cancer patients. |
PubMed ID | 30397360 |
PubMed Central ID | PMC6218528 |
Grant List | U10 CA047577 / CA / NCI NIH HHS / United States U10 CA031946 / CA / NCI NIH HHS / United States U10 CA033601 / CA / NCI NIH HHS / United States U10 CA180821 / CA / NCI NIH HHS / United States K07 CA140390 / CA / NCI NIH HHS / United States U10 CA180836 / CA / NCI NIH HHS / United States U10 CA180857 / CA / NCI NIH HHS / United States U10 CA041287 / CA / NCI NIH HHS / United States U10 CA180882 / CA / NCI NIH HHS / United States P01 CA142538 / CA / NCI NIH HHS / United States S10 OD018164 / OD / NIH HHS / United States U10 CA180838 / CA / NCI NIH HHS / United States U10 CA138561 / CA / NCI NIH HHS / United States |