Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a population-based case-control study.
Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a population-based case-control study.
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DOI：
10.1016/j.ygyno.2010.10.016
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发表时间：
2011-02
影响因子：
4.7
通讯作者：
Garcia-Closas M
中科院分区：
文献类型：
--
作者：
Lacey JV Jr;Yang H;Gaudet MM;Dunning A;Lissowska J;Sherman ME;Peplonska B;Brinton LA;Healey CS;Ahmed S;Pharoah P;Easton D;Chanock S;Garcia-Closas M
我们评估了PTEN、PIK 3CA、AKT 1、MLH 1和MSH 2基因的常见遗传变异是否与子宫内膜癌的风险相关。我们使用来自波兰一项基于人群的病例对照研究（佩奇）的数据，对417例病例和407例匹配对照进行了76个标记单核苷酸多态性基因分型。（tagSNPs;位于目的基因上游10 kb或下游5 kb内，在不同种族中次要等位基因频率>=5%，并且还没有被另一个tagSNP在r2>=0.80的LD处表示）在1316个基因中包括超过29，000个SNP的Illumina Custom Infinium iSelect测定上进行。对于单个SNPs，我们使用非条件logistic回归模型，调整年龄和地点，以生成比值比（OR）和95%置信区间（CI）。为了复制佩奇中的一个统计学显著关联，我们在英国的子宫内膜癌研究中，对1141例子宫内膜癌病例和2275例对照进行了独立的tagSNP基因分型。我们通过扩展的单倍型块和顺序单倍型扫描方法评估单倍型。PIK 3CA中的rs 2677764 tagSNP与佩奇中的子宫内膜癌统计学显著相关（OR=1.42，95%CI = 1.03-1.95; P=0.03），但与子宫内膜癌无关（OR=0.98，95%CI =0.82-1.17）。在佩奇中至少5%的病例和对照中观察到的25种单倍型中，仅PIK 3CA中的1种与子宫内膜癌统计学显著相关（OR=1.39，95%CI，1.00-1.93）。所有单倍型全局p值均为空。PTEN、PIK 3CA、AKT 1、MLH 1或MSH 2的常见遗传变异与子宫内膜癌无统计学显著相关性。
We assessed whether common genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2—genes that reportedly are frequently altered in endometrial cancer—was associated with risk of endometrial cancer. Using data from a population-based case-control study in Poland (PECS) of 417 cases and 407 matched controls, we genotyped 76 tagging single nucleotide polymorphisms (tagSNPs; located in or within 10kb upstream or 5kb downstream of the gene of interest, minor allele frequency>=5% among various ethnic groups, and not already represented by another tagSNP at a LD of r2>=0.80) on an Illumina Custom Infinium iSelect assay that included over 29,000 SNPs in 1316 genes. For individual SNPs, we used unconditional logistic regression models, adjusted for age and site, to generate odds ratios (ORs) and 95% confidence intervals (CIs). To replicate the one statistically significant association in PECS, we independently genotyped that tagSNP among 1141 endometrial cancer cases and 2275 controls from the SEARCH study in the UK. We assessed haplotypes via extended haplotype blocks and the sequential haplotype scan method. The rs2677764 tagSNP in PIK3CA was statistically significantly associated with endometrial cancer in PECS (OR=1.42, 95% CI, 1.03–1.95; P=0.03) but not SEARCH (OR=0.98, 95% CI=0.82–1.17). Of the 25 haplotypes observed in at least 5% of cases and controls in PECS, only 1, in PIK3CA, was statistically significantly associated with endometrial cancer (OR=1.39, 95% CI, 1.00–1.93). All haplotype global p-values were null. Common genetic variation in PTEN, PIK3CA, AKT1, MLH1, or MSH2 was not statistically significantly associated with endometrial cancer.
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