全基因组关联研究鉴定出与子宫内膜癌风险相关的常见变异。
Genome-wide association study identifies a common variant associated with risk of endometrial cancer.
机构信息
Division of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
出版信息
Nat Genet. 2011 May;43(5):451-4. doi: 10.1038/ng.812. Epub 2011 Apr 17.
Abstract
Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.
摘要
子宫内膜癌是发达国家女性生殖道最常见的恶性肿瘤。为了鉴定与子宫内膜癌风险相关的遗传变异，我们进行了一项全基因组关联研究，纳入了来自澳大利亚和英国的 1265 名子宫内膜癌患者（病例）和来自 Wellcome Trust Case Control Consortium 的 5190 名对照。我们比较了病例和对照中 519655 个 SNP 的基因型频率。在另外 3957 例病例和 6886 例对照中，对在第一阶段显示与子宫内膜癌相关证据的 47 个 SNP 进行了基因分型。我们在 17q12 附近（rs4430796，P = 7.1×10(-10)) 鉴定出一个与 HNF1B 接近的子宫内膜癌易感位点，该位点也与前列腺癌风险相关，并且与 2 型糖尿病风险呈负相关。
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本文引用的文献
1
A map of human genome variation from population-scale sequencing.
Nature. 2010 Oct 28;467(7319):1061-73. doi: 10.1038/nature09534.
2
Metabolic syndrome and endometrial cancer risk.
Ann Oncol. 2011 Apr;22(4):884-889. doi: 10.1093/annonc/mdq464. Epub 2010 Oct 11.
3
Risk factors in women 40 years of age and younger with endometrial carcinoma.
Acta Obstet Gynecol Scand. 2010 Oct;89(10):1326-30. doi: 10.3109/00016349.2010.515666.
4
Meta-analysis of genome-wide and replication association studies on prostate cancer.
Prostate. 2011 Feb 1;71(2):209-24. doi: 10.1002/pros.21235.
5
Substantially increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis of epidemiologic evidence in Japan.
J Diabetes Complications. 2010 Sep-Oct;24(5):345-53. doi: 10.1016/j.jdiacomp.2010.06.004. Epub 2010 Jul 24.
6
Mutations in the hepatocyte nuclear factor-1β (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations.
Am J Obstet Gynecol. 2010 Oct;203(4):364.e1-5. doi: 10.1016/j.ajog.2010.05.022. Epub 2010 Jul 15.
7
Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.
PLoS Genet. 2010 Jul 1;6(7):e1001012. doi: 10.1371/journal.pgen.1001012.
8
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
Nat Genet. 2010 Jul;42(7):579-89. doi: 10.1038/ng.609.
9
Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer.
BMC Cancer. 2010 Jun 22;10:315. doi: 10.1186/1471-2407-10-315.
10
Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.
PLoS One. 2010 May 28;5(5):e10858. doi: 10.1371/journal.pone.0010858.
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