Association of genetic variants of <i>TMEM135</i> and <i>PEX5</i> in the peroxisome pathway with cutaneous melanoma-specific survival.

Abstract

Background

Peroxisomes are ubiquitous and dynamic organelles that are involved in the metabolism of reactive oxygen species (ROS) and lipids. However, whether genetic variants in the peroxisome pathway genes are associated with survival in patients with melanoma has not been established. Therefore, our aim was to identify additional genetic variants in the peroxisome pathway that may provide new prognostic biomarkers for cutaneous melanoma (CM).

Methods

We assessed the associations between 8,397 common single-nucleotide polymorphisms (SNPs) in 88 peroxisome pathway genes and CM disease-specific survival (CMSS) in a two-stage analysis. For the discovery, we extracted the data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center (MDACC). We then replicated the results in another dataset from the Nurse Health Study (NHS)/Health Professionals Follow-up Study (HPFS).

Results

Overall, 95 (11.1%) patients in the MDACC dataset and 48 (11.7%) patients in the NHS/HPFS dataset died of CM. We found 27 significant SNPs in the peroxisome pathway genes to be associated with CMSS in both datasets after multiple comparison correction using the Bayesian false-discovery probability method. In stepwise Cox proportional hazards regression analysis, with adjustment for other covariates and previously published SNPs in the MDACC dataset, we identified 2 independent SNPs (TMEM135 rs567403 C>G and PEX5 rs7969508 A>G) that predicted CMSS (P=0.003 and 0.031, respectively, in an additive genetic model). The expression quantitative trait loci analysis further revealed that the TMEM135 rs567403 GG and PEX5 rs7969508 GG genotypes were associated with increased and decreased levels of mRNA expression of their genes, respectively.

Conclusions

Once our findings are replicated by other investigators, these genetic variants may serve as novel biomarkers for the prediction of survival in patients with CM.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.21037/atm-20-2117

Publication Info

Wang, Haijiao, Hongliang Liu, Wei Dai, Sheng Luo, Christopher I Amos, Jeffrey E Lee, Xin Li, Ying Yue, et al. (2021). Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival. Annals of translational medicine, 9(5). p. 396. 10.21037/atm-20-2117 Retrieved from https://hdl.handle.net/10161/22721.

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Scholars@Duke

Luo

Sheng Luo

Professor of Biostatistics & Bioinformatics
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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