A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.
A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.
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DOI：
10.1038/sj.bjc.6605966
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发表时间：
2010-12-07
影响因子：
8.8
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中科院分区：
文献类型：
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DNA修复缺陷在遗传性结直肠癌（CRC）中具有因果作用。碱基切除修复基因MUTYH的缺陷是MUTYH相关息肉病和CRC易感性的原因，是一种常染色体隐性遗传性状。许多报道表明MUTYH单等位基因变体是低风险等位基因。我们报告了一项大型协作荟萃分析，以评估和改进与双等位基因和单等位基因MUTYH变异相关的CRC风险估计，并调查年龄和性别对风险的影响。MUTYH基因型数据来自20565例病例和15524例对照。三个逻辑回归模型进行了测试：一个粗略的模型;调整年龄和性别;调整年龄，性别和研究。这三种模式产生了非常相似的结果。MUTYH双等位基因携带者的风险增加了28倍（95%置信区间（CI）：6.95-115）。G396 D和Y179 C/G396 D复合杂合子也观察到显著的双等位基因效应，变异Y179 C观察到边际单等位基因效应（比值比（OR）=1.34; 95%CI：1.00-1.80）。对提交的所有已发表和未发表数据集进行的汇总荟萃分析显示，MUTYH、G396 D和Y179 C存在双等位基因效应（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）和对于变体MUTYH（OR=1.16，95%CI：1.00-1.34）和单独的Y179 C（OR=1.34，95%CI：1.01-1.77）的边际单等位基因效应。总的来说，这项大型研究细化了与单等位基因和双等位基因MUTYH携带者相关的疾病风险估计。
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. 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. 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 A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02–23.2; OR=6.47, 95% CI: 2.33–18.0; OR=3.35, 95% CI: 1.14–9.89)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). Overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers.
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影响因子：
8.8
作者：
Colebatch, A.;Hitchins, M.;Ward, R. L.
通讯作者：
Ward, R. L.
影响因子：
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作者：
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Aaltonen, LA
影响因子：
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作者：
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Varesco, L
影响因子：
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作者：
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通讯作者：
Ranzani, GN
影响因子：
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作者：
D'Agostino, Vito G.;Minoprio, Anna;Mazzei, Filomena
通讯作者：
Mazzei, Filomena