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Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
Archambault, Alexi N; Su, Yu-Ru; Jeon, Jihyoun; Thomas, Minta; Lin, Yi; Conti, David V; Win, Aung Ko; Sakoda, Lori C; Lansdorp-Vogelaar, Iris; Peterse, Elisabeth F P; Zauber, Ann G; Duggan, David; Holowatyj, Andreana N; Huyghe, Jeroen R; Brenner, Hermann; Cotterchio, Michelle; Bézieau, Stéphane; Schmit, Stephanie L; Edlund, Christopher K; Southey, Melissa C; MacInnis, Robert J; Campbell, Peter T; Chang-Claude, Jenny; Slattery, Martha L; Chan, Andrew T; Joshi, Amit D; Song, Mingyang; Cao, Yin; Woods, Michael O; White, Emily; Weinstein, Stephanie J; Ulrich, Cornelia M; Hoffmeister, Michael; Bien, Stephanie A; Harrison, Tabitha A; Hampe, Jochen; Li, Christopher I; Schafmayer, Clemens; Offit, Kenneth; Pharoah, Paul D; Moreno, Victor; Lindblom, Annika; Wolk, Alicja; Wu, Anna H; Li, Li; Gunter, Marc J; Gsur, Andrea; Keku, Temitope O; Pearlman, Rachel; Bishop, D Timothy.
Afiliação
  • Archambault AN; Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
  • Su YR; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Jeon J; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
  • Thomas M; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Lin Y; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Conti DV; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Win AK; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Sakoda LC; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Research, Kaiser Permanente Northern California, Oakland, California.
  • Lansdorp-Vogelaar I; Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
  • Peterse EFP; Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
  • Zauber AG; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Duggan D; Translational Genomics Research Institute, An Affiliate of City of Hope, Phoenix, Arizona.
  • Holowatyj AN; Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.
  • Huyghe JR; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Res
  • Cotterchio M; Population Health and Prevention, Cancer Care Ontario, Toronto, Ontario, Canada.
  • Bézieau S; Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
  • Schmit SL; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Edlund CK; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Southey MC; Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
  • MacInnis RJ; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia; Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Campbell PT; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Slattery ML; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
  • Chan AT; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General H
  • Joshi AD; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Song M; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Cao Y; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri.
  • Woods MO; Memorial University of Newfoundland, Discipline of Genetics, St. John's, Newfoundland, Canada.
  • White E; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
  • Weinstein SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Ulrich CM; Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.
  • Hoffmeister M; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bien SA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Harrison TA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Hampe J; Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
  • Li CI; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Schafmayer C; Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Offit K; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
  • Pharoah PD; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Moreno V; Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
  • Lindblom A; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Wolk A; Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
  • Wu AH; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Li L; Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
  • Gunter MJ; Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Gsur A; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
  • Keku TO; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.
  • Pearlman R; Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
  • Bishop DT; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Gastroenterology ; 158(5): 1274-1286.e12, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31866242
ABSTRACT
BACKGROUND &

AIMS:

Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.

METHODS:

We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.

RESULTS:

Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.

CONCLUSIONS:

In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Predisposição Genética para Doença Limite: Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Gastroenterology Ano de publicação: 2020 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Predisposição Genética para Doença Limite: Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Gastroenterology Ano de publicação: 2020 Tipo de documento: Artigo