@article{2911093e4c3a45fca2dc194cf17da736,
title = "Genetic variation determines VEGF-A plasma levels in cancer patients",
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.",
author = "Federico Innocenti and Chen Jiang and Sibley, {Alexander B.} and Etheridge, {Amy S.} and Hatch, {Ace J.} and Stefanie Denning and Donna Niedzwiecki and Shterev, {Ivo D.} and Jiaxing Lin and Yoichi Furukawa and Michiaki Kubo and Kindler, {Hedy L.} and Auman, {J. Todd} and Venook, {Alan P.} and Hurwitz, {Herbert I.} and McLeod, {Howard L.} and Ratain, {Mark J.} and Raluca Gordan and Nixon, {Andrew B.} and Kouros Owzar",
note = "Funding Information: The authors would like to thank Kelli Hammond and Suzie Roth for editing this manuscript and Erin Connor for assisting with the genotyping of the CALGB 80203 patient samples. Karen L Mohlke is acknowledged for her contribution to the interpretation of the results. This work was supported by the National Cancer Institute of the National Institutes of Health (grant numbers U10 CA180821, U10 CA180882, U10 CA041287, U10 CA047577, U10 CA138561, U10 CA180836, U10 CA180838, U10 CA180857) and legacy grants from the Cancer and Leukemia Group B and the CALGB Statistical Data Center (U10 CA031946, U10 CA033601 to F.I., K.O., C.J., D.N., K.V.L., H.L.K., I.S., A.P.V.); National Institutes of Health (K07 CA140390-01 to F.I.) and (P01 CA142538 to F.I., J.L., K.O., R.G.). Research was also supported by the BioBank Japan Project, funded by the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese government to Y.N. and M.K.; and the National Institutes of Health Pharmacogenomics Research Network (PGRN) – RIKEN Global Alliance to F.I., K.O., Y.N., M.K., M.J.R., H.M.L. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-34506-4",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}