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Neumeyer; S. ; Hua, X.W.* ; Seibold, P.* ; Jansen, L.* ; Benner, A.* ; Burwinkel, B.* ; Halama, N.* ; Berndt, S.I.* ; Phipps, A.I.* ; Sakoda, L.C.* ; Schoen, R.E.* ; Slattery, M.L.* ; Chan, A.T.* ; Gala, M.* ; Joshi, A.D.* ; Ogino, S.* ; Song, M.Y.* ; Herpel, E.* ; Blaker, H.* ; Kloor, M.* ; Scherer, D.* ; Ulrich, A.* ; Ulrich, C.M.* ; Win, A.K.* ; Figueiredo, J.C.* ; Hopper, J.L.* ; Macrae, F.* ; Milne, R.L.* ; Giles, G.G.* ; Buchanan, D.D.* ; Peters, U.* ; Hoffmeister, M.* ; Brenner, H.* ; Newcomb, P.A. ; Chang-Claude, J.*

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

Cancer Epidemiol. Biomarkers Prev. 29, 2719-2728 (2020)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Factor-beta Receptor; Microsatellite Instability; Tgf-beta; Risk; Survival; Colon; Infiltration; Associations; Population; Frequency
ISSN (print) / ISBN 1055-9965
e-ISSN 1538-7755
Journal Cancer Epidemiology, Biomarkers & Prevention
Quellenangaben Volume: 29, Issue: 12, Pages: 2719-2728 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Grants Centers for Disease Control and Prevention National Program of Cancer Registries
German Federal Ministry of Education and Research
Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany
German Cancer Research Center
NCI Surveillance Epidemiology and End Results program
U.S. NCI
German Research Council
NIH/NCI Cancer Center Support Grant
VicHealth
Australian National Health and Medical Research Council
American Cancer Society
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): NCI, NIH, U.S. Department of Health and Human Services
NIH
Cancer Council Victoria