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Genetic Variants in the Regulatory T cell-Related Pathway and Colorectal Cancer Prognosis.
Neumeyer, Sonja; Hua, Xinwei; Seibold, Petra; Jansen, Lina; Benner, Axel; Burwinkel, Barbara; Halama, Niels; Berndt, Sonja I; Phipps, Amanda I; Sakoda, Lori C; Schoen, Robert E; Slattery, Martha L; Chan, Andrew T; Gala, Manish; Joshi, Amit D; Ogino, Shuji; Song, Mingyang; Herpel, Esther; Bläker, Hendrik; Kloor, Matthias; Scherer, Dominique; Ulrich, Alexis; Ulrich, Cornelia M; Win, Aung K; Figueiredo, Jane C; Hopper, John L; Macrae, Finlay; Milne, Roger L; Giles, Graham G; Buchanan, Daniel D; Peters, Ulrike; Hoffmeister, Michael; Brenner, Hermann; Newcomb, Polly A; Chang-Claude, Jenny.
Afiliação
  • Neumeyer S; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Hua X; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Seibold P; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Jansen L; School of Public Health, University of Washington, Seattle, Washington.
  • Benner A; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Burwinkel B; Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.
  • Halama N; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Berndt SI; Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Phipps AI; Department of Gynecology and Obstetrics, Molecular Biology of Breast Cancer, University of Heidelberg, Heidelberg, Germany.
  • Sakoda LC; Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
  • Schoen RE; Tissue Imaging and Analysis Center, National Center for Tumor Diseases, BIOQUANT, University of Heidelberg, Heidelberg, Germany.
  • Slattery ML; Institute for Immunology, University Hospital Heidelberg, Heidelberg, Germany.
  • Chan AT; Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
  • Gala M; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Joshi AD; Epidemiology Department, University of Washington, Seattle, Washington.
  • Ogino S; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Song M; Division of Research, Kaiser Permanente Northern California, Oakland, California.
  • Herpel E; Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • Bläker H; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
  • Kloor M; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Scherer D; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Ulrich A; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Ulrich CM; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Win AK; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Figueiredo JC; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Hopper JL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Macrae F; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Milne RL; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • Giles GG; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • Buchanan DD; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Peters U; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Hoffmeister M; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Brenner H; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Newcomb PA; NCT Tissue Bank, National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Chang-Claude J; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Cancer Epidemiol Biomarkers Prev ; 29(12): 2719-2728, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33008876
ABSTRACT

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.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Alemanha

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: Alemanha
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