Gaudet Mia M, Lacey James V, Lissowska Jolanta, Peplonska Beata, Brinton Louise A, Chanock Stephen, Garcia-Closas Montserrat
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA,
Hum Genet. 2008 Mar;123(2):155-62. doi: 10.1007/s00439-007-0454-8. Epub 2008 Jan 3.
Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP) in the 5'UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer. To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to capture >80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96-1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and 1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias.
基于细胞色素P450 17α羟化酶（CYP17）在类固醇和非类固醇激素生物合成调节中的作用，怀疑其基因变异与子宫内膜癌风险相关。一些研究报道的CYP17与较高雌二醇水平之间的关联表明，CYP17 5'非翻译区（UTR）中一个T到C单核苷酸多态性（SNP）（rs743572）的C等位基因可能与激素相关癌症风险增加有关。然而，五项相对较小规模的子宫内膜癌流行病学研究报告称，携带rs743572 C等位基因的女性患子宫内膜癌的风险降低。为了检验这种关联，我们对rs743572和其他八个单倍型标签SNP（htSNP）进行了基因分型，在波兰一项基于人群的研究中，对497例子宫内膜癌病例和1024名对照进行了检测，这些htSNP估计可捕获CYP17中>80%的变异。未发现rs743572（每个C等位基因：比值比=1.12，95%可信区间0.96 - 1.30；P趋势=0.15）、单个htSNP或扩展单倍型存在显著关联（全局P值=0.60）。当我们将先前发表的研究数据与我们自己的研究数据（共1004例子宫内膜癌病例和1907名对照）合并时，我们观察到rs743572与子宫内膜癌关联的汇总估计值存在显著的研究异质性，以及发表偏倚的证据。总之，我们的数据与先前报道的rs743572与子宫内膜癌风险降低之间的关联不一致，也与其他单倍型标签多态性不一致。有必要在合作研究中进行进一步评估，以确认CYP17常见变异与子宫内膜癌风险之间潜在的微弱关联，并解决发表偏倚问题。
