Inherited DNA-Repair Defects in Colorectal Cancer

American Journal of Human Genetics
Saud H AlDubayanEliezer M Van Allen

Abstract

Colorectal cancer (CRC) heritability has been estimated to be around 30%. However, mutations in the known CRC-susceptibility genes explain CRC risk in fewer than 10% of affected individuals. Germline mutations in DNA-repair genes (DRGs) have recently been reported in CRC, but their contribution to CRC risk is largely unknown. We evaluated the gene-level germline mutation enrichment of 40 DRGs in 680 unselected CRC individuals and 27,728 ancestry-matched cancer-free adults. Significant findings were then examined in independent cohorts of 1,661 unselected CRC individuals and 1,456 individuals with early-onset CRC. Of the 680 individuals in the discovery set, 31 (4.56%) individuals harbored germline pathogenic mutations in known CRC-susceptibility genes, and another 33 (4.85%) individuals had DRG mutations that have not been previously associated with CRC risk. Germline pathogenic mutations in ATM and PALB2 were enriched in both the discovery (OR = 2.81 and p = 0.035 for ATM and OR = 4.91 and p = 0.024 for PALB2) and validation (OR = 2.97 and adjusted p = 0.0013 for ATM and OR = 3.42 and adjusted p = 0.034 for PALB2) sets. Biallelic loss of ATM was evident in all individuals with matched tumor profiling. CRC individuals also had ...Continue Reading

Citations

Jan 25, 2019·JAMA Oncology·Saud H AlDubayanUNKNOWN Regeneron Genetics Center (RGC) Research Team
Feb 5, 2019·Molecular Oncology·Nicole M ReillyAlberto Bardelli
Mar 31, 2019·International Journal of Cancer. Journal International Du Cancer·Lídia FeliubadalóUNKNOWN Catalan Hereditary Cancer Group
Oct 13, 2019·Cold Spring Harbor Molecular Case Studies·Jamie L MaciaszekChimene A Kesserwan
Dec 17, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xin YangMarc Tischkowitz
Mar 17, 2020·Familial Cancer·Brandie HealdUNKNOWN Collaborative Group of the Americas on Inherited Gastrointestinal Cancer
Oct 13, 2019·Mutagenesis·Stephanie A SchubertTom van Wezel
Dec 18, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Amin H NassarGuru Sonpavde
Nov 20, 2019·Current Treatment Options in Gastroenterology·Benjamin SternMaria Baker
Dec 16, 2018·Breast Cancer Research and Treatment·Laura Duran-LozanoOrland Diez
Aug 14, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Holly LaDucaJill S Dolinsky
Jun 2, 2020·Frontiers in Cell and Developmental Biology·Chaoqin ShenBaoqin Xuan
Jan 17, 2020·Balkan Journal of Medical Genetics : BJMG·M Staninova-StojovskaA J Dimovski
Jun 27, 2020·Journal of Clinical Medicine·Mariona TerradasLaura Valle
Oct 1, 2020·International Journal of Cancer. Journal International Du Cancer·Elena V PreobrazhenskayaEvgeny N Imyanitov
Nov 18, 2020·JAMA : the Journal of the American Medical Association·Saud H AlDubayanEliezer M Van Allen
Jun 21, 2019·Cancer Immunology Research·Carino GurjaoMarios Giannakis
Dec 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sabrina ArenaAlberto Bardelli
Mar 18, 2021·International Journal of Cancer. Journal International Du Cancer·Hafdis T HelgadottirAnnika Lindblom
May 1, 2021·Cancers·Beate Köberle, Sarah Schoch
Jun 9, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G MauriA Sartore-Bianchi
Nov 23, 2021·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Yung-Shuo Kao, James Cheng-Chung Wei
Jan 15, 2022·Cancer Communications·Caroline Moraes BeltramiSilvia Regina Rogatto

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