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

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.

Duke Scholars

Author Jennifer Freedman Medicine, Medical Oncology

Author Patricia Gripka Moorman Family Medicine and Community Health, Prevention Research

Author Terry Hyslop Biostatistics & Bioinformatics, Division of Translational Bi ...

Author Daniel James George Medicine, Medical Oncology

Author Steven Patierno Medicine, Medical Oncology

Author Qingyi Wei Population Health Sciences

Altmetric Attention Stats

Dimensions Citation Stats

Published In

Int J Cancer

DOI

10.1002/ijc.30787

EISSN

1097-0215

Publication Date

August 15, 2017

Volume

141

Issue

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

APA

Chicago

ICMJE

MLA

NLM

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.