Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis
Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis
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DOI：
10.1038/sj.bjc.6604170
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发表时间：
2008-01-22
影响因子：
8.8
通讯作者：
Berchuck, A.
中科院分区：
文献类型：
--
作者：
Pearce, C. L.;Wu, A. H.;Berchuck, A.
有证据表明黄体酮在侵袭性上皮性卵巢癌的病因学中发挥作用。因此，参与调节黄体酮途径的基因可能是对该疾病易感性的候选基因。先前的研究表明，孕激素受体基因（PGR）的遗传变异可能与卵巢癌风险相关，但结果并不一致。我们建立了一个国际联盟，汇集来自许多卵巢癌病例对照研究的资源和数据，努力识别影响风险的变异。在这项研究中，检查了三个 PGR 单核苷酸多态性 (SNP)，之前的数据表明它们会影响卵巢癌风险。这些是 +331 C/T (rs10895068)、PROGINS (rs1042838) 和 30 变体 (rs608995)。该分析共纳入 12 项病例对照研究的 4788 例卵巢癌病例和 7614 例对照。使用无条件逻辑回归对每个 SNP 与卵巢癌风险之间的关联进行建模，并报告两侧 P 值。总体而言，卵巢癌的风险与所研究的三种变异中的任何一种均无关。然而，在组织病理学亚型分析中，我们发现子宫内膜样卵巢癌的风险与 PROGINS 等位基因之间存在统计学上显着的关联（n = 651，OR = 1.17，95% CI = 1.01-1.36，P = 0.036）。我们还观察到子宫内膜样卵巢癌风险与+331C/T 变异之间存在关联的边界证据（n 725 例；OR = 0.80，95% CI 0.62-1.04，P = 0.100）。这些数据表明，虽然 PGR 中的这三种变异总体上与卵巢癌无关，但 PROGINS 变异可能在子宫内膜样卵巢癌风险中发挥适度作用。
There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 30 variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n = 651, OR = 1.17, 95% CI = 1.01-1.36, P = 0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n 725 cases; OR = 0.80, 95% CI 0.62-1.04, P = 0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.