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000163862 1001_ $$0P:(DE-He78)bc9ae72f1f27696587eeb1c81e48fb69$$aNeumeyer, Sonja$$b0$$eFirst author
000163862 245__ $$aGenetic variants in the regulatory T cell related pathway and colorectal cancer prognosis
000163862 260__ $$aPhiladelphia, Pa.$$bAACR$$c2020
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000163862 500__ $$a2020 Dec;29(12):2719-2728#EA:C020#LA:C020#
000163862 520__ $$aBackground: 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.
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000163862 7001_ $$00000-0003-2114-2975$$aHua, Xinwei$$b1
000163862 7001_ $$0P:(DE-He78)fd17a8dbf8d08ea5bb656dfef7398215$$aSeibold, Petra$$b2
000163862 7001_ $$0P:(DE-He78)bbfe0ebad1e3b608bca2b49d4f86bd09$$aJansen, Lina$$b3
000163862 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b4
000163862 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, Barbara$$b5
000163862 7001_ $$aHalama, Niels$$b6
000163862 7001_ $$aBerndt, Sonja I.$$b7
000163862 7001_ $$aPhipps, Amanda I.$$b8
000163862 7001_ $$00000-0002-0900-5735$$aSakoda, Lori C.$$b9
000163862 7001_ $$00000-0001-7153-2766$$aSchoen, Robert E$$b10
000163862 7001_ $$00000-0002-1655-6543$$aSlattery, Martha L.$$b11
000163862 7001_ $$aChan, Andrew T.$$b12
000163862 7001_ $$aGala, Manish$$b13
000163862 7001_ $$aJoshi, Amit D.$$b14
000163862 7001_ $$00000-0002-3909-2323$$aOgino, Shuji$$b15
000163862 7001_ $$aSong, Mingyang$$b16
000163862 7001_ $$aHerpel, Esther$$b17
000163862 7001_ $$aBläker, Hendrik$$b18
000163862 7001_ $$0P:(DE-He78)028ee60cca729028708496826f077b58$$aKloor, Matthias$$b19
000163862 7001_ $$aScherer, Dominique$$b20
000163862 7001_ $$00000-0003-1469-2186$$aUlrich, Alexis$$b21
000163862 7001_ $$aUlrich, Cornelia M$$b22
000163862 7001_ $$00000-0002-2794-5261$$aWin, Aung K$$b23
000163862 7001_ $$aFigueiredo, Jane C.$$b24
000163862 7001_ $$aHopper, John L.$$b25
000163862 7001_ $$aMacrae, Finlay$$b26
000163862 7001_ $$aMilne, Roger L$$b27
000163862 7001_ $$00000-0003-4946-9099$$aGiles, Graham G.$$b28
000163862 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D.$$b29
000163862 7001_ $$aPeters, Ulrike$$b30
000163862 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b31
000163862 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b32
000163862 7001_ $$aNewcomb, Polly A.$$b33
000163862 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b34$$eLast author
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