title: Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study.
abstract: OBJECTIVE
  Whereas it has conclusively been demonstrated that biallelic MutY human homolog (MYH) mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. Characterization of MYH-associated CRC is critical to identify individuals who might benefit from preventive strategies. This prospective, multicenter, case-control, population-based study was aimed at (1) establishing the CRC risk associated with specific germline MYH mutations and (2) devising a set of clinical criteria to identify MYH carriers among newly diagnosed CRC.
  
  
  METHODS
  Genotyping for Y165C and G382D was performed by TaqMan technology. Single-stranded conformation polymorphism analysis was performed in heterozygotes to screen for mutations in the entire gene. All individuals were re-screened for any additional pathogenic variant.
  
  
  RESULTS
  Biallelic and monoallelic MYH mutations were found in 8 (0.7%) and 19 (1.7%) of 1116 CRC patients, respectively. None of the 934 control subjects carried biallelic mutations, whereas 22 (2.3%) of them were monoallelic carriers. In a meta-analysis including all previous case-control studies, monoallelic MYH carriers were not at increased risk for CRC (odds ratio, 1.11; 95% confidence interval, 0.90-1.37), although a significant association was found with the Y165C mutation in either homozygotes or heterozygotes (odds ratio, 1.67; 95% confidence interval, 1.17-2.40). Furthermore, presence of more than 15 synchronous colorectal adenomas or CRC diagnosed before the age of 50 years was the most effective set of criteria for the identification of biallelic MYH mutation carriers.
  
  
  CONCLUSIONS
  This study proposes the first set of clinical criteria designed to identify CRC patients with biallelic MYH mutations, and it argues against an increased risk for monoallelic carriers.
authors: Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Ciberehd, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Balaguer
authors: Sergi
authors: S
authors: Castellví-Bel
authors: Antoni
authors: A
authors: Castells
authors: Montserrat
authors: M
authors: Andreu
authors: Jenifer
authors: J
authors: Muñoz
authors: Javier P
authors: JP
authors: Gisbert
authors: Xavier
authors: X
authors: Llor
authors: Rodrigo
authors: R
authors: Jover
authors: Rafael
authors: R
authors: de Cid
authors: Victòria
authors: V
authors: Gonzalo
authors: Xavier
authors: X
authors: Bessa
authors: Rosa M
authors: RM
authors: Xicola
authors: Elisenda
authors: E
authors: Pons
authors: Cristina
authors: C
authors: Alenda
authors: Artemio
authors: A
authors: Payá
authors: Josep M
authors: JM
authors: Piqué
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016001:Confidence Intervals; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase