Genetic variants in the regulatory T cell-related pathway and colorectal cancer prognosis

Background: High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiat...

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Hauptverfasser: Neumeyer, Sonja (VerfasserIn) , Hua, Xinwei (VerfasserIn) , Seibold, Petra Beate (VerfasserIn) , Jansen, Lina (VerfasserIn) , Benner, Axel (VerfasserIn) , Burwinkel, Barbara (VerfasserIn) , Halama, Niels (VerfasserIn) , Berndt, Sonja I. (VerfasserIn) , Phipps, Amanda I. (VerfasserIn) , Sakoda, Lori C. (VerfasserIn) , Schoen, Robert E. (VerfasserIn) , Slattery, Martha L. (VerfasserIn) , Chan, Andrew T. (VerfasserIn) , Gala, Manish (VerfasserIn) , Joshi, Amit D. (VerfasserIn) , Ogino, Shuji (VerfasserIn) , Song, Mingyang (VerfasserIn) , Herpel, Esther (VerfasserIn) , Bläker, Hendrik (VerfasserIn) , Kloor, Matthias (VerfasserIn) , Scherer, Dominique (VerfasserIn) , Ulrich, Alexis (VerfasserIn) , Ulrich, Cornelia (VerfasserIn) , Win, Aung K. (VerfasserIn) , Figueiredo, Jane C. (VerfasserIn) , Hopper, John L. (VerfasserIn) , Macrae, Finlay (VerfasserIn) , Milne, Roger L. (VerfasserIn) , Giles, Graham G. (VerfasserIn) , Buchanan, Daniel D. (VerfasserIn) , Peters, Ulrike (VerfasserIn) , Hoffmeister, Michael (VerfasserIn) , Brenner, Hermann (VerfasserIn) , Newcomb, Polly A. (VerfasserIn) , Chang-Claude, Jenny (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 2, 2020
In: Cancer epidemiology, biomarkers & prevention
Year: 2020, Jahrgang: 29, Heft: 12, Pages: 2719-2728
ISSN:1538-7755
DOI:10.1158/1055-9965.EPI-20-0714
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1055-9965.EPI-20-0714
Verlag, lizenzpflichtig, Volltext: https://cebp.aacrjournals.org/content/29/12/2719
Volltext
Verfasserangaben:Sonja Neumeyer, Xinwei Hua, Petra Seibold, Lina Jansen, Axel Benner, Barbara Burwinkel, Niels Halama, Sonja I. Berndt, Amanda I. Phipps, Lori C. Sakoda, Robert E. Schoen, Martha L. Slattery, Andrew T. Chan, Manish Gala, Amit D. Joshi, Shuji Ogino, Mingyang Song, Esther Herpel, Hendrik Bläker, Matthias Kloor, Dominique Scherer, Alexis Ulrich, Cornelia M. Ulrich, Aung K. Win, Jane C. Figueiredo, John L. Hopper, Finlay Macrae, Roger L. Milne, Graham G. Giles, Daniel D. Buchanan, Ulrike Peters, Michael Hoffmeister, Hermann Brenner, Polly A. Newcomb, and Jenny Chang-Claude

MARC

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520 |a Background: High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis. - Methods: In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC). - Results: A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer-specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74-0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68-0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed. - Conclusions: Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients. - Impact: The implicated genes warrant further investigation. 
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