Common variation in a long non-coding RNA gene modulates variation of circulating TGF-

Authors

• Julia C F Quintanilha
• Alexander B Sibley
• Yingmiao Liu
• Donna Niedzwiecki
• Susan Halabi
• Layne Rogers
• Bert O'Neil
• Hedy Kindler
• William Kelly
• Alan Venook
• Howard L McLeod
• Mark J Ratain
• Andrew B Nixon
• Federico Innocenti
• Kouros Owzar

Publication/Presentation Date

12-4-2023

Abstract

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC).The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings.

RESULTS: The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel

CONCLUSIONS: This study has provided evidence of a novel

Published In/Presented At

Quintanilha, J. C. F., Sibley, A. B., Liu, Y., Niedzwiecki, D., Halabi, S., Rogers, L., O'Neil, B., Kindler, H., Kelly, W., Venook, A., McLeod, H. L., Ratain, M. J., Nixon, A. B., Innocenti, F., & Owzar, K. (2023). Common variation in a long non-coding RNA gene modulates variation of circulating TGF-β2 levels in metastatic colorectal cancer patients (Alliance). medRxiv : the preprint server for health sciences, 2023.12.04.23298815. https://doi.org/10.1101/2023.12.04.23298815

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

38106038

Department(s)

Administration and Leadership

Document Type

Article