Abstract：
BACKGROUND: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 A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89)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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
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,Küry S,Bézieau S,Buecher B,Ellis NA,Peterlongo P,Offit K,Aaltonen Ldoi
10.1038/sj.bjc.6605966subject
Has Abstractpub_date
2010-12-07 00:00:00pages
1875-84issue
12eissn
0007-0920issn
1532-1827pii
6605966journal_volume
103pub_type
杂志文章,meta分析abstract：BACKGROUND:Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. METHODS:From the General Practi...
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