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Title: Association between germline variants and somatic mutations in colorectal cancer
Author: Barfield, Richard
Qu, Conghui
Steinfelder, Robert S.
Zeng, Chenjie
Harrison, Tabitha A.
Brezina, Stefanie
Buchanan, Daniel D.
Campbell, Peter T.
Casey, Graham
Gallinger, Steven
Giannakis, Marios
Gruber, Stephen B.
Gsur, Andrea
Hsu, Li
Huyghe, Jeroen R.
Moreno Aguado, Víctor
Newcomb, Polly A.
Ogino, Shuji
Phipps, Amanda I.
Slattery, Martha L.
Thibodeau, Stephen N.
Trinh, Quang M.
Toland, Amanda E.
Hudson, Thomas J.
Sun, Wei
Zaidi, Syed H.
Peters, Ulrike
Keywords: Càncer colorectal
Polimorfisme genètic
Colorectal cancer
Genetic polymorphisms
Issue Date: 17-Jun-2022
Publisher: Springer Science and Business Media LLC
Abstract: Colorectal cancer (CRC) is a heterogeneous disease with evidence of distinct tumor types that develop through different somatically altered pathways. To better understand the impact of the host genome on somatically mutated genes and pathways, we assessed associations of germline variations with somatic events via two complementary approaches. We first analyzed the association between individual germline genetic variants and the presence of non-silent somatic mutations in genes in 1375 CRC cases with genome-wide SNPs data and a tumor sequencing panel targeting 205 genes. In the second analysis, we tested if germline variants located within previously identified regions of somatic allelic imbalance were associated with overall CRC risk using summary statistics from a recent large scale GWAS (n similar or equal to 125 k CRC cases and controls). The first analysis revealed that a variant (rs78963230) located within a CNA region associated with TLR3 was also associated with a non-silent mutation within gene FBXW7. In the secondary analysis, the variant rs2302274 located in CDX1/PDGFRB frequently gained/lost in colorectal tumors was associated with overall CRC risk (OR = 0.96, p = 7.50e-7). In summary, we demonstrate that an integrative analysis of somatic and germline variation can lead to new insights about CRC.
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It is part of: Scientific Reports, 2022, vol. 12, num. 1, p. 10207
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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