Colorectal cancer and inherited mutations in base-excision repair.
Polyposis associated with mutations in the gene MUTYH is an autosomal recessive syndrome characterised by the development of multiple colorectal adenomas and cancer. It is the first cancer-predisposition disorder to be associated with defects in the pathway of base-excision repair. We review our knowledge to date of the disease, discuss base-excision repair in relation to cellular defence against oxidative damage, and give an overview of the molecular genetics and clinicopathological features of tumours associated with MUTYH mutations. No longer a research finding, genetic testing for MUTYH is now a necessary part of molecular diagnosis in familial cancer clinics throughout Australia and the UK. Current recommendations for the screening and management of the disease are also discussed.
Chow
Elizabeth
E
Royal Melbourne Hospital, Victoria, Australia.
Thirlwell
Christina
C
Macrae
Finlay
F
Lipton
Lara
L
D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D003937:Diagnosis, Differential; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase