Common genetic variation in the sex hormone metabolic pathway and endometrial cancer risk: pathway-based evaluation of candidate genes
Common genetic variation in the sex hormone metabolic pathway and endometrial cancer risk: pathway-based evaluation of candidate genes
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DOI：
10.1093/carcin/bgp328
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发表时间：
2010-05-01
期刊：
影响因子：
4.7
通讯作者：
Garcia-Closas, Montserrat
中科院分区：
文献类型：
--
作者：
Yang, Hannah P.;Gonzalez Bosquet, Jesus;Garcia-Closas, Montserrat
背景。雌激素在子宫内膜癌发生中起重要作用，这表明性激素代谢途径中常见的基因变异可能与子宫内膜癌风险相关。为了支持这一观点，CYP19A1 [细胞色素 P450 (CYP)，家族 19，亚家族，多肽 1] 的变异与循环雌激素水平和子宫内膜癌风险相关。有人提出与其他基因变异的关联，但研究结果并不一致。方法。我们在波兰进行的一项基于人群的病例对照研究中，使用标记方法检查了 36 个性激素相关基因，该研究对 417 例子宫内膜癌病例和 407 例对照进行了研究。我们使用顺序单倍型扫描、可变大小滑动窗口和自适应排序截断乘积（ARTP）方法评估了这些基因与子宫内膜癌风险相关的常见变异。结果。在我们的病例对照研究中，与子宫内膜癌风险最强的关联是 AR（雄激素受体；ARTP P = 0.006）。多位点分析还确定了 AR 和 CYP19A1 中先前确定的易感性位点周围感兴趣区域的边界。我们没有找到证据表明先前报道的该途径中的候选单核苷酸多态性与子宫内膜癌风险之间存在一致的关联。讨论。总之，我们确定了 AR 和 CYP19A1 中的区域，这些区域有利于进一步评估未来单倍型和更大研究人群中的精细作图研究中与子宫内膜癌风险相关的区域。
Background. 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. Methods. 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. Results. 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. Discussion. 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.