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Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.

Publication ,  Journal Article
Wang, Y; Freedman, JA; Liu, H; Moorman, PG; Hyslop, T; George, DJ; Lee, NH; Patierno, SR; Wei, Q
Published in: Int J Cancer
August 15, 2017

Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, and two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness-related genes and racial disparities in susceptibility to prostate cancer. We evaluated associations of single-nucleotide polymorphisms (SNPs) in 25 stemness-related genes with prostate cancer risk in 1,609 cases and 2,550 controls of non-Hispanic whites (4,934 SNPs) and 1,144 cases and 1,116 controls of African descendants (5,448 SNPs) with correction by false discovery rate ≤0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1, WNT1, MET and EGFR) that were significantly associated with prostate cancer risk, of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs showed heterogeneity in susceptibility between these two racial groups. In addition, 13 SNPs in MET and one in ALDH1A1 were found only in African descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454 and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r2  > 0.6) were predicted to regulate RNA splicing. These variants may serve as novel biomarkers for racial disparities in prostate cancer risk.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2017

Volume

141

Issue

4

Start / End Page

731 / 743

Location

United States

Related Subject Headings

  • White People
  • RNA Splicing
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Wang, Y., Freedman, J. A., Liu, H., Moorman, P. G., Hyslop, T., George, D. J., … Wei, Q. (2017). Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer. Int J Cancer, 141(4), 731–743. https://doi.org/10.1002/ijc.30787
Wang, Yanru, Jennifer A. Freedman, Hongliang Liu, Patricia G. Moorman, Terry Hyslop, Daniel J. George, Norman H. Lee, Steven R. Patierno, and Qingyi Wei. “Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.Int J Cancer 141, no. 4 (August 15, 2017): 731–43. https://doi.org/10.1002/ijc.30787.
Wang Y, Freedman JA, Liu H, Moorman PG, Hyslop T, George DJ, et al. Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer. Int J Cancer. 2017 Aug 15;141(4):731–43.
Wang, Yanru, et al. “Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.Int J Cancer, vol. 141, no. 4, Aug. 2017, pp. 731–43. Pubmed, doi:10.1002/ijc.30787.
Wang Y, Freedman JA, Liu H, Moorman PG, Hyslop T, George DJ, Lee NH, Patierno SR, Wei Q. Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer. Int J Cancer. 2017 Aug 15;141(4):731–743.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2017

Volume

141

Issue

4

Start / End Page

731 / 743

Location

United States

Related Subject Headings

  • White People
  • RNA Splicing
  • Prostatic Neoplasms
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease