RT Journal Article
SR Electronic
T1 Genetic Variants in the Regulatory T cell–Related Pathway and Colorectal Cancer Prognosis
JF Cancer Epidemiology Biomarkers & Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
SP 2719
OP 2728
DO 10.1158/1055-9965.EPI-20-0714
VO 29
IS 12
A1 Neumeyer, Sonja
A1 Hua, Xinwei
A1 Seibold, Petra
A1 Jansen, Lina
A1 Benner, Axel
A1 Burwinkel, Barbara
A1 Halama, Niels
A1 Berndt, Sonja I.
A1 Phipps, Amanda I.
A1 Sakoda, Lori C.
A1 Schoen, Robert E.
A1 Slattery, Martha L.
A1 Chan, Andrew T.
A1 Gala, Manish
A1 Joshi, Amit D.
A1 Ogino, Shuji
A1 Song, Mingyang
A1 Herpel, Esther
A1 Bläker, Hendrik
A1 Kloor, Matthias
A1 Scherer, Dominique
A1 Ulrich, Alexis
A1 Ulrich, Cornelia M.
A1 Win, Aung K.
A1 Figueiredo, Jane C.
A1 Hopper, John L.
A1 Macrae, Finlay
A1 Milne, Roger L.
A1 Giles, Graham G.
A1 Buchanan, Daniel D.
A1 Peters, Ulrike
A1 Hoffmeister, Michael
A1 Brenner, Hermann
A1 Newcomb, Polly A.
A1 Chang-Claude, Jenny
YR 2020
UL http://cebp.aacrjournals.org/content/29/12/2719.abstract
AB 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.