Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/179342
Title: Genetic architectures of proximal and distal colorectal cancer are partly distinct
Author: Huyghe, Jeroen R.
Harrison, Tabitha A.
Bien, Stephanie A.
Hampel, Heather
Figueiredo, Jane C.
Schmit, Stephanie L.
Conti, David V.
Chen, Sai
Qu, Conghui
Lin, Yi
Barfield, Richard
Moreno, Lorena
Cross, Amanda J.
Riboli, Elio
Wu, Anna H.
Murphy, Neil
Nassir, Rami
Offit, Kenneth
Ogino, Shuji
Perduca, Vittorio
Tangen, Catherine M.
Kundaje, Anshul
Panico, Salvatore
Parfrey, Patrick S.
Potter, John D.
Pearlman, Rachel
Van Guelpen, Bethany
Visvanathan, Kala
Prentice, Ross L.
Qi, Lihong
Baron, John A.
Raskin, Leon
Arndt, Volker
Weinstein, Stephanie J.
Schafmayer, Clemens
Schoen, Robert E.
Levine, David M.
Seminara, Daniela
Diergaarde, Brenda
Thibodeau, Stephen N.
Thomas, Duncan C.
Van Duijnhoven, Fränzel J. B.
Trichopoulou, Antonia
Perez Cornago, Aurora
Vodicka, Pavel
Vodickova, Ludmila
Arnau Collell, Coral
Vymetalkova, Veronika
White, Emily
Wolk, Alicja
Bishop, D. Timothy
Woods, Michael O.
Abecasis, Gonçalo R.
Nickerson, Deborah A.
Brezina, Stefanie
Scacheri, Peter C.
Casey, Graham
Gruber, Stephen B.
Hsu, Li
Moreno Aguado, Víctor
Gallinger, Steven J.
Agudo, Antonio
Campbell, Peter T.
Hayes, Richard B.
Newcomb, Polly A.
Duggan, David
Peters, Ulrike
Gunter, Marc J.
Banbury, Barbara L.
Harlid, Sophia
Imaz, Liher
Sakoda, Lori C.
Kang, Hyun Min
Huang, Wen-yi
Boehm, Juergen
Schumacher, Fredrick R.
Slattery, Martha L.
Gala, Manish
Toland, Amanda E.
Buch, Stephan
Albanes, Demetrius
Alonso, M. Henar
Gsur, Andrea
Anderson, Kristin
Gauderman, W. James
Bassik, Michael C.
Berndt, Sonja I.
Hsu, Wan-ling
Bézieau, Stéphane
Boeing, Heiner
Boutron Ruault, Marie Christine
Keku, Temitope O.
Brenner, Hermann
Buchanan, Daniel D.
Burnett Hartman, Andrea
Lejbkowicz, Flavio
Caan, Bette J.
Carr, Prudence R.
Castells Garangou, Antoni
Castellví Bel, Sergi
Chan, Andrew T.
Phipps, Amanda I.
Haile, Robert W.
Lindor, Noralane M.
Chang Claude, Jenny
Chanock, Stephen J.
Curtis, Keith R.
De La Chapelle, Albert
Rennert, Hedy S.
Hudson, Thomas J.
Easton, Douglas F.
English, Dallas R.
Giles, Graham G.
Feskens, Edith J. M.
Su, Yu-ru
Kooperberg, Charles
Goodman, Phyllis J.
Grady, William M.
Pharoah, Paul D. P.
Grove, John S.
Li, Christopher I.
Hampe, Jochen
Hoffmeister, Michael
Rennert, Gad
Hopper, John L.
Platz, Elizabeth A.
Jenab, Mazda
Jenkins, Mark A.
Song, Mingyang
Joshi, Amit D.
Kühn, Tilman
Küry, Sébastien
Ulrich, Cornelia M.
Le Marchand, Loic
Li, Li
Lieb, Wolfgang
Weigl, Korbinian
Lindblom, Annika
Männistö, Satu
Markowitz, Sanford D.
Milne, Roger L.
Keywords: Medicina preventiva
Càncer colorectal
Genètica
Preventive medicine
Colorectal cancer
Genetics
Issue Date: 25-Feb-2021
Publisher: BMJ
Abstract: Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Note: Reproducció del document publicat a: https://doi.org/10.1136/gutjnl-2020-321534
It is part of: Gut, 2021, vol. 70, num. 7, p. 1325-1334
URI: http://hdl.handle.net/2445/179342
Related resource: https://doi.org/10.1136/gutjnl-2020-321534
ISSN: 1468-3288
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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