@article{f30c9f11318b4c58ba63cd62793f4efe,
title = "Association between germline variants and somatic mutations in colorectal cancer",
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≃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.",
author = "Richard Barfield and Conghui Qu and Steinfelder, {Robert S.} and Chenjie Zeng and Harrison, {Tabitha A.} and Stefanie Brezina and Buchanan, {Daniel D.} and Campbell, {Peter T.} and Graham Casey and Steven Gallinger and Marios Giannakis and Gruber, {Stephen B.} and Andrea Gsur and Li Hsu and Huyghe, {Jeroen R.} and Victor Moreno and Newcomb, {Polly A.} and Shuji Ogino and Phipps, {Amanda I.} and Slattery, {Martha L.} and Thibodeau, {Stephen N.} and Trinh, {Quang M.} and Toland, {Amanda E.} and Hudson, {Thomas J.} and Wei Sun and Zaidi, {Syed H.} and Ulrike Peters",
note = "Funding Information: This project was a part of Richard Barfield{\textquoteright}s post-doc work at Fred Hutchinson Cancer Research Center. Richard Barfield{\textquoteright}s contributions were supported through a post-doctoral position at the University of Washington funded by the NIH/NCI Grant T32 CA094880. Amanda Toland was funded by the NIH/NCI Grant R01 CA215151. Li Hsu was partially funded by the NIH/NCI Grant R01 CA189532. Jeroen R Huyghe was partially funded by the NIH/NCI Grant R21 CA230486. Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, U01 CA164930, R01201407, R01 CA1762772). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-14408-2",
language = "English (US)",
volume = "12",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}
