Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.
Mutations in the base excision repair gene MYH have recently been shown to confer recessive susceptibility to colorectal adenomas and carcinomas. To evaluate the contribution of germline MYH mutations to early-onset colorectal cancer, we screened a series of 358 unselected early-onset cases for germline changes in the coding sequence of the gene. Two cases harbored biallelic germline mutations (0.6%; 95% CI = 0.06-2.0) and 8 single MYH mutations (2.2%; 95% CI = 0.9-4.4). Both cases harboring biallelic MYH mutations had multiple polyps but not profuse polyposis. All cases had distally sited tumors. No biallelic mutations were detected among 354 controls. These results confirm that biallelic MYH mutations confer susceptibility to colorectal cancer but are unlikely to account for more than 3% of early-onset colorectal cancer.
Fleischmann
Christina
C
Section of Cancer Genetics, Institute of Cancer Research, Surrey, United Kingdom.
Peto
Julian
J
Cheadle
Jeremy
J
Shah
Bindiya
B
Sampson
Julian
J
Houlston
Richard S
RS
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000328:Adult; D017668:Age of Onset; D022981:Allelic Imbalance; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000378:metabolism; D006113:United Kingdom
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase