Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Stotz, M.
Cancer stem cell gene variants and their prognostic value in adjuvant setting of colon cancer
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2018. pp. 76 [OPEN ACCESS]


Autor*innen der Med Uni Graz:
Gerger Armin
Renner Wilfried
Stöger Herbert

Background: Growing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of cancer entities including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single nucleotid polymorphisms (SNPs) in stem cell related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III. Methods: Data from 599 consecutive patients with colon cancer stage II and III, treated between 1995 and 2011 at a single centre, were evaluated retrospectively. Genomic DNA was extracted from paraffin-embedded normal tissue distant from the tumor to obtain germline DNA. Allelic distribution of polymorphisms was tested for deviation from Hardy–Weinberg equilibrium using ¿2-test. The association of polymorphisms with time to recurrence (TTR) and overall survival (OS) was analyzed using Kaplan–Meier curves and compared by log-rank test. Case-wise deletion for missing polymorphisms was used in univariable and multivariable analyses. Results: CD44 rs187115 showed a statistically significant association with TTR – patients carrying at least one G allele had a significant reduced risk of recurrence compared to patients with the homozygous A/A variant (HR 0.67, 95% CI 0.48-0.94, p=0.019). CD44 rs13347 showed a statistically significant association with OS. Patients carrying at least one T allele in rs13347 had a significantly reduced risk of death compared to patients with the homozygous C/C variant (HR 0.61, 95% CI 0.41-0.92, p=0.019). None of the other investigated polymorphisms (CD44 rs187116, CD44 rs7116432, CD44 rs353639, DPP4 rs2268889, DPP4 rs3788979, DPP4 rs7608798 and CD133 rs2240688) was associated with either TTR or OS. Conclusion: Our data show that the germline variants rs13347 and rs187115 in the stem cell gene CD44 are prognostically relevant in stage II and III colon cancer patients.

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