Genetic architectures of proximal and distal colorectal cancer are partly distinct
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00555712" target="_blank" >RIV/68378041:_____/21:00555712 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11140/21:10425761 RIV/00216208:11110/21:10425761
Result on the web
<a href="https://gut.bmj.com/content/70/7/1325" target="_blank" >https://gut.bmj.com/content/70/7/1325</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1136/gutjnl-2020-321534" target="_blank" >10.1136/gutjnl-2020-321534</a>
Alternative languages
Result language
angličtina
Original language name
Genetic architectures of proximal and distal colorectal cancer are partly distinct
Original language description
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.nnDesign 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.nnResults We identified 13 loci that reached genome-wide significance (p<5x10(-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.nnConclusion 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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
<a href="/en/project/LO1503" target="_blank" >LO1503: BIOMEDIC</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Gut
ISSN
0017-5749
e-ISSN
1468-3288
Volume of the periodical
70
Issue of the periodical within the volume
7
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
1325-1334
UT code for WoS article
000667248900015
EID of the result in the Scopus database
2-s2.0-85101809425