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Polymorphisms in oxidative stress pathway genes and prostate cancer risk

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Abstract

Purpose

Age-related factors including oxidative stress play an important role in prostate carcinogenesis. We hypothesize that germline single-nucleotide polymorphisms (SNPs) in oxidative stress pathway are associated with prostate cancer (PCa) risk. In this study, we aim to examine which of these SNPs is associated with PCa.

Methods

Participants included in this analyses came from the “Genetic Susceptibility, Environment and Prostate Cancer Risk Study” conducted at the Veterans Affairs Portland Health Care System. After applying exclusion criteria, 231 PCa cases and 382 prostate biopsy-negative controls who had genotyping data on twenty-two single-nucleotide polymorphisms (SNPs) in six genes (MAPK14, NRF2, CAT, GPX1, GSTP1, SOD2, and XDH) associated with oxidative stress pathway were included in the analyses. The genotyping of SNPs was conducted by the Illumina BeadXpress VeraCode platform. We investigated these SNPs in relation to overall and aggressive PCa risk using logistic regression models controlling for relevant covariates.

Results

One SNP in the MAPK14 (rs851023) was significantly associated with incident PCa risk. Compared to men carrying two copies of allele A, the presence of one or two copies of the G allele was associated with decreased risk of PCa [OR (95% CI) 0.19 (0.06–0.51)]. There was no statistically significant association between other SNPs in the NRF2, CAT, GPX1, GSTP1, SOD2, and XDH genes and PCa risk.

Conclusions

The MAPK14 gene SNP rs851023 was associated with PCa and aggressive PCa risk after multiple comparison adjustment. Further studies in other populations or functional studies are needed to validate the finding.

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Abbreviations

ANOVA:

Analysis of variance

BIC:

Bayesian information criterion

BMI:

Body mass index

95% CI:

95% confidence interval

GSEP:

Genetic Susceptibility, Environment and Prostate Cancer Risk

NCI:

National Cancer Institute

OHSU:

Oregon Health & Science University

PIN:

Prostatic intraepithelial neoplasia

PSA:

Prostate-specific antigen

PSAD:

Prostate-specific antigen density

SE:

Standard Error

VAPHCS:

VA Portland Health Care System

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Acknowledgments

We greatly appreciate all the veterans and their family members who contributed their time and effort to join the Genetic Susceptibility, Environment and Prostate Cancer Risk (GSEP) study. Gratitude is expressed to our large list of collaborators and providers of tools to make this project successful; use of Case Western University’s Genetic Risk Easy Assessment Tool (GREAT) was provided by Dr. Louise Acheson; Oregon Clinical and Translational Research Institute’s (OCTRI) Biomedical Informatics Program was instrumental in tying all of our electronic questionnaires together into one HIPAA-compliant portal; VAPHCS phlebotomy staff helped us collect research specimens and allowing laboratory space for saliva collection; OCTRI’s Clinical and Translational Research Center (CTRC) Core Laboratory processed, analyzed, and stored subjects’ biological specimens; genotyping was conducted by iGenix in Seattle, Washington. Dr. Shannon’s current and previous research coordinators spent large amounts of time with our numerous in-person and over-the-phone participants in support of this study, assuring quality data collection as well as close, personal attention to our nation’s veterans and their family members choosing to join this study. We are also grateful to VAPHCS Urology Nurses and Operative Care staff for supporting coordinators’ recruitment of research participants.

Funding

Research reported in this publication was supported by the Veterans Affairs’ Biomedical Laboratory Research and Development Merit Review Award, VA Portland Health Care System (VAPHCS), and by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128. Clinical Trial Registration’s clinicaltrials.gov identifier: NCT01013129. This work was directly supported by the Veterans Affairs’ Biomedical Laboratory Research and Development Merit Review Award, and Oregon Health & Science University/Oregon State University Cancer Prevention and Control Initiative (2017-Horizon-Knight-11).

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Authors and Affiliations

  1. Division of Hematology and Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Zhenzhen Zhang

  2. Department of Statistics, Oregon State University, Corvallis, OR, 97331, USA

    Duo Jiang & Andy Dang

  3. Department of Biostatistics, University of Kentucky, Lexington, KY, 40536, USA

    Chi Wang

  4. Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA

    Chi Wang

  5. Urology Section, Veterans Affairs Portland Health Care System, Portland, OR, 97239, USA

    Mark Garzotto & Ryan Kopp

  6. Department of Urology, Oregon Health & Science University, Portland, OR, 97239, USA

    Mark Garzotto & Ryan Kopp

  7. Oregon Clinical and Translational Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Beth Wilmot

  8. Department of Medical and Clinical Informatics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Beth Wilmot

  9. Department of Dermatology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Philippe Thuillier

  10. OHSU-PSU School of Public Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code CR 145, Portland, OR, 97239, USA

    Philippe Thuillier, Amy Palma, Paige E. Farris & Jackilen Shannon

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  1. Zhenzhen Zhang
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Correspondence to Jackilen Shannon.

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Zhang, Z., Jiang, D., Wang, C. et al. Polymorphisms in oxidative stress pathway genes and prostate cancer risk. Cancer Causes Control 30, 1365–1375 (2019). https://doi.org/10.1007/s10552-019-01242-7

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  • DOI: https://doi.org/10.1007/s10552-019-01242-7

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