Genetic architectures of proximal and distal colorectal cancer are partly distinct.
Adult
Age Distribution
Age of Onset
Aged
Aged, 80 and over
Alleles
Case-Control Studies
Cecum
Colon
Colon, Ascending
Colon, Descending
Colon, Sigmoid
Colon, Transverse
Colonic Neoplasms
/ diagnosis
Female
Genetic Heterogeneity
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Rectal Neoplasms
/ diagnosis
Risk Factors
White People
/ genetics
Young Adult
cancer genetics
cancer susceptibility
colon carcinogenesis
colorectal cancer
genetic polymorphisms
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
23
04
2020
revised:
26
11
2020
accepted:
18
12
2020
pubmed:
27
2
2021
medline:
11
1
2022
entrez:
26
2
2021
Statut:
ppublish
Résumé
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. 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. We identified 13 loci that reached genome-wide significance (p<5×10 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.
Identifiants
pubmed: 33632709
pii: gutjnl-2020-321534
doi: 10.1136/gutjnl-2020-321534
pmc: PMC8223655
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1325-1334Subventions
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA137088
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164930
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008C
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207371
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA059045
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197735
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037429
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182883
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA158141
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA151993
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA191312
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA206110
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA143237
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201407
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA042182
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA158141
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States
Organisme : NCI NIH HHS
ID : K07 CA190673
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008I
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA071789
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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