Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Gynecol Oncol. 2011 Feb;120(2):167-73. doi: 10.1016/j.ygyno.2010.10.016. Epub 2010 Nov 20.
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 10 kb upstream or 5 kb 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 r(2) >=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.
我们评估了 PTEN、PIK3CA、AKT1、MLH1 和 MSH2 基因中的常见遗传变异，这些基因在子宫内膜癌中经常发生改变，是否与子宫内膜癌的风险相关。
利用波兰基于人群的病例对照研究（PECS）中的 417 例病例和 407 例匹配对照的数据，我们使用 Illumina Custom Infinium iSelect 检测方法对 76 个标记单核苷酸多态性（tagSNP；位于目标基因的上下游 10 kb 内或 5 kb 内，在不同种族中次要等位基因频率>=5%，且在 LD 为 r(2)>=0.80 时不被另一个 tagSNP 代表）进行基因分型，该检测方法包括 1316 个基因中的超过 29000 个 SNPs。对于单个 SNPs，我们使用无条件逻辑回归模型，根据年龄和地点进行调整，生成比值比（OR）和 95%置信区间（CI）。为了复制 PECS 中一个具有统计学意义的关联，我们在英国的 SEARCH 研究中独立对该 tagSNP 进行了 1141 例子宫内膜癌病例和 2275 例对照的基因分型。我们通过扩展单倍型块和顺序单倍型扫描方法评估单倍型。
PIK3CA 中的 rs2677764 tagSNP 在 PECS 中与子宫内膜癌具有统计学显著相关性（OR=1.42，95%CI，1.03-1.95；P=0.03），但在 SEARCH 中无统计学显著相关性（OR=0.98，95%CI=0.82-1.17）。在 PECS 中至少 5%的病例和对照中观察到的 25 种单倍型中，只有一种位于 PIK3CA 中，与子宫内膜癌具有统计学显著相关性（OR=1.39，95%CI，1.00-1.93）。所有单倍型全局 p 值均为零。
PTEN、PIK3CA、AKT1、MLH1 或 MSH2 中的常见遗传变异与子宫内膜癌无统计学显著相关性。
