Journal Article

DKFZ-2020-02096

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic variants in the regulatory T cell related pathway and colorectal cancer prognosis

Neumeyer, S. (First author)DKFZ* ; Hua, X. ; Seibold, P.DKFZ* ; Jansen, L.DKFZ* ; Benner, A.DKFZ* ; Burwinkel, B.DKFZ* ; 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. ; Herpel, E. ; Bläker, H. ; Kloor, M.Extern* ; 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.DKFZ* ; Brenner, H.DKFZ* ; Newcomb, P. A. ; Chang-Claude, J. (Last author)DKFZ*

2020
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-20-0714

Abstract: Background: High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer (CRC) 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 CRC prognosis.Methods: In a prospective German cohort of 3 593 CRC patients, we assessed the association of 771 SNPs in 58 T-reg related genes with overall and CRC-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated since tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2 047 CRC patients of the International Survival Analysis in Colorectal cancer Consortium (ISACC).Results: A significant association of the TGFBR3 SNP rs7524066 with more favorable CRC-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 CRC patients.Impact: The implicated genes warrant further investigation.

Note: 2020 Dec;29(12):2719-2728#EA:C020#LA:C020#

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. C060 Biostatistik (C060)
5. Molekulare Epidemiologie (C080)
6. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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