Genetic variation determines VEGF-A plasma levels in cancer patients.

TitleGenetic variation determines VEGF-A plasma levels in cancer patients.
Publication TypeJournal Article
Year of Publication2018
AuthorsInnocenti, 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
JournalSci Rep
Volume8
Issue1
Pagination16332
Date Published2018 11 05
ISSN2045-2322
KeywordsAdult, 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.

DOI10.1038/s41598-018-34506-4
Alternate JournalSci Rep
Original PublicationGenetic variation determines VEGF-A plasma levels in cancer patients.
PubMed ID30397360
PubMed Central IDPMC6218528
Grant ListU10 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