Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck.

Abstract

Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; Ptrend  = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; Ptrend  = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies.

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Citation

Published Version (Please cite this version)

10.1002/mc.22801

Publication Info

Han, Peng, Hongliang Liu, Qiong Shi, Zhensheng Liu, Jesse D Troy, Walter T Lee, Jose P Zevallos, Guojun Li, et al. (2018). Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck. Molecular carcinogenesis, 57(6). pp. 784–793. 10.1002/mc.22801 Retrieved from https://hdl.handle.net/10161/18510.

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Scholars@Duke

Troy

Jesse David Troy

Associate Professor of Biostatistics & Bioinformatics

I am the Associate Director of Graduate Studies for the Master of Biostatistics program. I am also an instructor in the Clinical Research Training Program. I work on research studies in cancer therapeutics and palliative care at the Duke Cancer Institute.

Lee

Walter T Lee

Professor of Head and Neck Surgery & Communication Sciences

Global Health, Virtue-Based Professional Development and Leadership, Device Development for Cancer Detection, otolaryngology, ENT, Head and Neck Cancer

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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