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@ARTICLE{Frsti:307497,
author = {A. Försti$^*$ and B. Miao$^*$ and A. Kumar$^*$ and D.
Dymerska Zaremba and M. Marciniak and J. Lubinski and K.
Hemminki$^*$},
title = {{F}amilial colorectal cancer: search for novel
predisposition genes.},
journal = {Human genomics},
volume = {nn},
issn = {1473-9542},
address = {London [u.a.]},
publisher = {Henry Stewart Publ.},
reportid = {DKFZ-2026-00002},
pages = {nn},
year = {2025},
note = {#EA:B062#LA:C020#LA:Z999# / epub},
abstract = {Family history of colorectal cancer (CRC) and multiple
primary CRCs in a single person may indicate inherited CRC
predisposition.In the present study, we performed whole
exome/genome sequencing on germline DNA from at least two
CRC cases in 19 families and from family members with a
double primary CRC from seven additional families. We used a
set of in silico predictions in combination with a STRING
protein-protein interaction and pathway analysis to identify
the most likely variants predisposing to CRC.We identified
Cell cycle/DNA repair and TGFβ signaling/Focal
adhesion/Extracellular matrix organization pathways as
highly significant protein-protein interaction networks.
Variants in the APCDD1, CYBA, PTK7 and SRC genes were
identified in more than one family, and they were shown to
dysregulate basic cellular functions, potentially leading to
cancer development. Most variants were private to a family,
and each family had more than one candidate variant,
suggesting a synergistic or polygenic mode of inheritance.
This hypothesis, as well as validation of the identified
variants and pathways and their functional consequences,
need confirmation by other family-based studies.Different
types of family-based analyses together with in silico
predictions are helpful to identify candidate genes and
pathways for CRC predisposition.},
keywords = {Colorectal cancer (Other) / Familial cancer (Other) /
Genetic predisposition (Other) / Multiple primaries (Other)},
cin = {B062 / HD01 / D250 / A360 / C020 / Z999},
ddc = {570},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)D250-20160331 / I:(DE-He78)A360-20160331 /
I:(DE-He78)C020-20160331 / I:(DE-He78)Z999-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41469725},
doi = {10.1186/s40246-025-00901-y},
url = {https://inrepo02.dkfz.de/record/307497},
}