Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants Theodoratou E; Campbell H; Tenesa A; Houlston R; Webb E; Lubbe S; Broderick P; Gallinger S; Croitoru EM; Jenkins MA; Win AK; Cleary SP; Koessler T; Pharoah PD; Kury S; Bezieau S; Buecher B; Ellis NA; Peterlongo P; Offit K; Aaltonen LA; Enholm S; Lindblom A; Zhou XL; Tomlinson IP; Moreno V; Blanco I; Capella G; Barnetson R; Porteous ME; Dunlop MG; Farrington SMBr J Cancer 2010[Dec]; 103 (12): 1875-84BACKGROUND: defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants and investigate age and sex influence on risk. METHODS: MUTYH genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. RESULTS: all three models produced very similar results. MUTYH bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95-115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00-1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89) and marginal mono-allelic effect for variants MUTYH (OR=1.16, 95% CI: 1.00-1.34) and Y179C alone (OR=1.34, 95% CI: 1.01-1.77). CONCLUSIONS: overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers.|Adult[MESH]|Aged[MESH]|Colorectal Neoplasms/etiology/*genetics[MESH]|DNA Glycosylases/*genetics[MESH]|Female[MESH]|Genetic Predisposition to Disease[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Mutation[MESH]|Risk Factors[MESH] |