Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival
With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose. The tribbles homologue 1 gene ( ) has recently shown to have...
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Published in | Frontiers in genetics Vol. 9; p. 428 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
04.10.2018
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Subjects | |
Online Access | Get full text |
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Summary: | With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose. The tribbles homologue 1 gene (
) has recently shown to have a role in prostate tumorigenesis and data-mining of prostate cancer expression data confirmed clinical significance of
in prostate cancer. For the first time, a polymorphic microsatellite in this gene was studied for its potential association with prostate cancer risk and aggressiveness. Genomic DNA was extracted from a cohort of 1,152 prostate cancer patients and 1,196 cancer-free controls and the TTTTG-
microsatellite was genotyped. The socio-demographic and clinical characteristics were analyzed using the non-parametric
-test and two-way ANOVA. Association of the TTTTG-
microsatellite and prostate cancer risk and aggressiveness were analyzed by binary logistic regression and confirmed by bootstrapping. Total and prostate cancer mortality was analyzed using the Kaplan Meier test. Genotype and allele correlation with TRIB1 mRNA levels was analyzed using the non-parametric Kolmogorov-Smirnov test. To predict the effect that the TTTTG-
polymorphisms had on the mRNA structure, the
RNA folding predictor tool, mfold, was used. By analyzing the publicly available data, we confirmed a significant over-expression of
in prostate cancer compared to other cancer types, and an over-expression in prostate cancerous tissue compared to adjacent benign. Three alleles (three-five repeats) were observed for TTTTG-
. The three-repeat allele was associated with prostate cancer risk at the allele (OR = 1.16;
= 0.044) and genotypic levels (OR = 1.70;
= 0.006) and this association was age-independent. The four-repeat allele was inversely associated with prosatet cancer risk (OR = 0.57;
< 0.0001).
expression was upregulated in tumors when compared to adjacent cancer-free tissue but was not allele specific.
analysis suggested that the TTTTG-
alleles may alter TRIB1 mRNA structure. In summary, the three-repeat allele was significantly associated with prostate cancer risk, suggesting a biomarker potential for this microsatellite to predict prostate cancer. Further studies are needed to elucidate the functional role of this microsatellite in regulating
expression, perhaps by affecting the TRIB1 mRNA structure and stability. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Cancer Genetics, a section of the journal Frontiers in Genetics Reviewed by: Weikuan Gu, The University of Tennessee Health Science Center, United States; Sharon E. Johnatty, QIMR Berghofer Medical Research Institute, Australia The participants of the Australian Prostate Cancer BioResource are listed in the Acknowledgements section. Edited by: Logan Walker, University of Otago, New Zealand |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2018.00428 |