Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.
Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.
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DOI：
10.1016/j.canep.2012.04.006
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发表时间：
2012-10
影响因子：
2.6
通讯作者：
Zeleniuch-Jacquotte, Anne
中科院分区：
文献类型：
--
作者：
Lundin, Eva;Wirgin, Isaac;Lukanova, Annekatrin;Afanasyeva, Yelena;Krogh, Vittorio;Axelsson, Tomas;Hemminki, Kari;Clendenen, Tess V.;Arslan, Alan A.;Ohlson, Nina;Sieri, Sabina;Roy, Nirmal;Koenig, Karen L.;Idahl, Annika;Berrino, Franco;Toniolo, Paolo;Hallmans, Goran;Foersti, Asta;Muti, Paola;Lenner, Per;Shore, Roy E.;Zeleniuch-Jacquotte, Anne
关键词：
雌激素和孕激素在子宫内膜癌发展中的作用已有充分记录。很少有研究探讨性激素相关基因的遗传变异与子宫内膜癌风险的关系。我们在 391 例病例（诊断时 92% 为绝经后）和 712 例单独匹配的对照组中进行了一项嵌套在三个队列中的病例对照研究，以检查子宫内膜癌风险与激素相关基因多态性的关联。我们还在一项横断面分析中检查了这些多态性与性激素和性激素结合球蛋白（SHBG）循环水平的关联，该分析包括 596 名健康绝经后献血妇女（来自这项巢式病例对照研究和三个队列之一的乳腺癌巢式病例对照研究的对照）。调整子宫内膜癌风险因素后，CYP19 中 rs4775936 的 A 等位基因显着相关（ORper 等位基因 = 1.22，95% CI = 1.01–1.47，ptrend = 0.04），而 rs10046 的 T 等位基因与子宫内膜癌风险增加略有相关（ORper 等位基因 = 1.20，95% CI = 0.99 – 1.45， 趋势 = 0.06)。 PGR rs1042838 也与风险略有相关（ORper 等位基因 = 1.25，95% CI = 0.96–1.61，ptrend = 0.09）。其他多态性（即 CYP1B1 rs1800440 和 rs1056836、UGT1A1 rs8175347、SHBG rs6259 和 ESR1 rs2234693）没有发现显着关联。 Rs8175347 与绝经后雌二醇、游离雌二醇和雌酮水平显着相关，而 rs6259 与 SHBG 和雌二醇显着相关。我们的研究结果支持 CYP19 基因变异（可能还有 PGR）与子宫内膜癌风险之间的关联。
The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (ORper allele = 1.22, 95% CI = 1.01–1.47, ptrend = 0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (ORper allele = 1.20, 95% CI = 0.99 – 1.45, ptrend = 0.06). PGR rs1042838 was also marginally associated with risk (ORper allele = 1.25, 95% CI = 0.96–1.61, ptrend = 0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.
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影响因子：
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作者：
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通讯作者：
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