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.
Royal Melbourne Hospital, Victoria, Australia.
Elizabeth
E
Chow
Christina
C
Thirlwell
Finlay
F
Macrae
Lara
L
Lipton
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