Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival

Haijiao Wang; Hongliang Liu; Wei Dai; Sheng Luo; Christopher I Amos; Jeffrey E Lee; Xin Li; Ying Yue; Hongmei Nan; Qingyi Wei

doi:10.21037/atm-20-2117

Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival

Ann Transl Med. 2021 Mar;9(5):396. doi: 10.21037/atm-20-2117.

Authors

Haijiao Wang^{1

2

3}, Hongliang Liu^{2

3}, Wei Dai⁴, Sheng Luo⁵, Christopher I Amos⁶, Jeffrey E Lee⁷, Xin Li⁸, Ying Yue¹, Hongmei Nan⁸, Qingyi Wei^{2

3

9}

Affiliations

¹ Department of Gynecology Oncology, The First Hospital of Jilin University, Changchun, Jilin, China.
² Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
³ Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
⁴ Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁵ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.
⁶ Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
⁷ Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
⁹ Department of Medicine, Duke University School of Medicine, Durham, NC, USA.

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.

Keywords: Cutaneous melanoma (CM); expression quantitative trait loci; melanoma-specific survival; peroxisome; single-nucleotide polymorphism (SNP).

Abstract

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