Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA.
Carcinogenesis. 2010 May;31(5):827-33. doi: 10.1093/carcin/bgp328. Epub 2010 Jan 6.
Estrogen plays a major role in endometrial carcinogenesis, suggesting that common variants of genes in the sex hormone metabolic pathway may be related to endometrial cancer risk. In support of this view, variants in CYP19A1 [cytochrome P450 (CYP), family 19, subfamily A, polypeptide 1] have been associated with both circulating estrogen levels and endometrial cancer risk. Associations with variants in other genes have been suggested, but findings have been inconsistent.
We examined 36 sex hormone-related genes using a tagging approach in a population-based case-control study of 417 endometrial cancer cases and 407 controls conducted in Poland. We evaluated common variation in these genes in relation to endometrial cancer risk using sequential haplotype scan, variable-sized sliding window and adaptive rank-truncated product (ARTP) methods.
In our case-control study, the strongest association with endometrial cancer risk was for AR (androgen receptor; ARTP P = 0.006). Multilocus analyses also identified boundaries for a region of interest in AR and in CYP19A1 around a previously identified susceptibility loci. We did not find evidence for consistent associations between previously reported candidate single-nucleotide polymorphisms in this pathway and endometrial cancer risk.
In summary, we identified regions in AR and CYP19A1 that are of interest for further evaluation in relation to endometrial cancer risk in future haplotype and subsequent fine mapping studies in larger study populations.
雌激素在子宫内膜癌的发生中起着重要作用，这表明性激素代谢途径中的基因常见变体可能与子宫内膜癌风险有关。支持这一观点的是，CYP19A1（细胞色素 P450（CYP）家族 19 亚家族 A 多肽 1）中的变体与循环雌激素水平和子宫内膜癌风险都有关。其他基因中的变体也与风险相关，但研究结果并不一致。
我们在波兰进行的一项基于人群的病例对照研究中，使用标记方法研究了 36 个与性激素相关的基因，该研究共纳入了 417 例子宫内膜癌病例和 407 例对照。我们使用连续单体型扫描、可变大小滑动窗口和自适应秩截断乘积（ARTP）方法，评估了这些基因中的常见变异与子宫内膜癌风险的关系。
在我们的病例对照研究中，与子宫内膜癌风险最强相关的是 AR（雄激素受体；ARTP P = 0.006）。多基因分析还确定了 AR 和 CYP19A1 中感兴趣区域的边界，这些区域围绕先前确定的易感基因座。我们没有发现该途径中先前报道的候选单核苷酸多态性与子宫内膜癌风险之间存在一致关联的证据。
总之，我们确定了 AR 和 CYP19A1 中的区域，这些区域在未来更大的研究人群中进行单体型和随后的精细映射研究时，与子宫内膜癌风险的相关性值得进一步评估。
