DDR genes in cancer

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There are at least 450 genes associated with DDR [1, 2]. Some identified examples of DDR genes known to be involved in cancer are shown in the table below. Several DNA repair and DDR signalling proteins are associated with familial cancer predisposition syndromes (due to inactivating germline mutations) and with somatic mutations in sporadic cancers [1-4].

DDR deregulation may lead to cancer through various mechanisms [5-10].

  • Dysregulation of one or more DDR pathways
  • Increased levels of replication stress
  • Increased levels of endogenous damage
  • Some combination of the above, and/or sustained by the application of anticancer therapies such as radiation or chemotherapy

Table 5: Examples of DDR genes associated in cancer

DNA repair
Cancer-associated mutations
BER OGG1 Renal, breast and lung cancer
XRCC1 Non-small cell lung cancer
NER ERCC1 Lung and skin cancer, and glioma
XP Xeroderma pigmentosum predisposing to skin cancer. Also increased risk of bladder and lung cancer
MMR MSH2, MLH1 Lynch syndrome predisposing to colorectal cancer as well as endometrial, ovarian, stomach, hepatobiliary tract, upper urinary tract, brain and skin cancer
HRR BRCA1, BRCA2 Increased risk of breast, ovarian, prostate, pancreatic, as well as gastrointestinal and haematological cancer, and melanoma
FANC Group of proteins associated with Fanconi anaemia predisposing to squamous cell carcinomas of the head and neck and acute myeloid leukaemia (e.g. FANCA, FANCB)
NHEJ KU70 Breast, colorectal and lung cancer
KU80 Lung cancer
Cell cycle
ATM Ataxia-telangiectasia predisposing to leukaemia, breast and pancreatic cancer
ATR Leukaemia, lymphoma, gastric and endometrial cancer
P53 Li-Fraumeni syndrome

Table includes both germline and somatically derived mutations.
BER, base excision repair; HRR, homologous recombination repair; NER, nucleotide excision repair; NHEJ, non-homologous end joining; MMR, mismatch repair.


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  4. Jeggo PA, Pearl LH, Carr AM. DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer 2016; 16: 35-42.
  5. Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 2008; 26: 3785-3790.
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  7. Farmer H, McCabe N, Lord CJ et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434: 917-921.
  8. Bryant HE, Schultz N, Thomas HD et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913-917.
  9. Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 2012; 12: 801-817.
  10. Lucchesi JC. Synthetic lethality and semi-lethality among functionally related mutants of Drosophila melanfgaster. Genetics 1968; 59: 37-44.
Last update: 25 July 2019