Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival.

Abstract

The complement system plays an important role in the innate and adaptive immunity, complement components mediate tumor cytolysis of antibody-based immunotherapy, and complement activation in the tumor microenvironment may promote tumor progression or inhibition, depending on the mechanism of action. In the present study, we conducted a two-phase analysis of two independently published genome-wide association studies (GWASs) for associations between genetic variants in a complement-related immunity gene-set and overall survival of non-small cell lung cancer (NSCLC). The GWAS dataset from Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was used as the discovery, and multivariate Cox proportional hazards regression with false-positive report probability for multiple test corrections were performed to evaluate associations between 14,699 single-nucleotide polymorphisms (SNPs) in 111 genes and survival of 1,185 NSCLC patients. The identified significant SNPs in a single-locus analysis were further validated with 984 NSCLC patients in the GWAS dataset from the Harvard Lung Cancer Susceptibility (HLCS) Study. The results showed that two independent, potentially functional SNPs in two genes (VWF rs73049469 and ITGB2 rs3788142) were significantly associated with NSCLC survival, with a combined hazards ratio (HR) of 1.22 [95% confidence interval (CI) = 1.07-1.40, P = 0.002] and 1.16 (1.07-1.27, 6.45 × 10-4 ), respectively. Finally, we performed expression quantitative trait loci (eQTL) analysis and found that survival-associated genotypes of VWF rs73049469 were also significantly associated with mRNA expression levels of the gene. These results indicated that genetic variants of the complement-related immunity genes might be predictors of NSCLC survival, particularly for the short-term survival, possibly by modulating the expression of genes involved in the host immunity.

Department

Description

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Citation

Published Version (Please cite this version)

10.1002/ijc.31896

Publication Info

Qian, Danwen, Hongliang Liu, Xiaomeng Wang, Jie Ge, Sheng Luo, Edward F Patz, Patricia G Moorman, Li Su, et al. (2019). Potentially functional genetic variants in the complement-related immunity gene-set are associated with non-small cell lung cancer survival. International journal of cancer, 144(8). pp. 1867–1876. 10.1002/ijc.31896 Retrieved from https://hdl.handle.net/10161/18498.

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Scholars@Duke

Luo

Sheng Luo

Professor of Biostatistics & Bioinformatics
Patz

Edward F. Patz

James and Alice Chen Distinguished Professor of Radiology

There are numerous ongoing clinical studies primarily focused on the early detection of cancer.

The basic science investigations in our laboratory concentration on three fundamental translational areas,

1) Development of molecular imaging probes - We have used several different approaches to develop novel imaging probes that characterize and phenotype tumors.

2) Discovery of novel lung cancer biomarkers - We explored the use of proteomics, autoantibodies, and genomics to discover blood and tissue biomarkers for early cancer detection and phenotyping of cancer.

3) Host response to cancer - We study the native immune response to tumors as this may provide cues to relevant diagnostic and therapeutic targets. Most recently we have focused on intratumoral lymphocytes and their specific tumor antigens.

 

Moorman

Patricia Gripka Moorman

Professor Emeritus in Family Medicine and Community Health

Dr. Moorman's research focuses on the epidemiology of women's health issues. Her work includes research on ovarian cancer, breast cancer and hysterectomy. Areas of particular interest include disparities in cancer risk factors and outcomes and the effects of hysterectomy on ovarian function.  As part of the Duke Evidence Synthesis group, she has also been involved in systematic reviews and meta-analyses related to ovarian cancer, breast cancer and infertility.

Wei

Qingyi Wei

Professor in Population Health Sciences

Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and variations in cell death. He is Editor-in-Chief of the open access journal "Cancer Medicine" and Associate Editor-in-Chief of the International Journal of Molecular Epidemiology and Genetics.

Area of Expertise: Epidemiology


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