Polymorphisms of estrogen receptor α gene in endometrial cancer
Polymorphisms of estrogen receptor α gene in endometrial cancer
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DOI：
10.1016/s0006-291x(02)02248-9
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发表时间：
2002-09-27
影响因子：
3.1
通讯作者：
Dahiya, R
中科院分区：
文献类型：
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作者：
Sasaki, M;Tanaka, Y;Dahiya, R
雌激素受体α（ER α）基因多态性与子宫内膜癌的发生有关。为了验证这一假设，研究了ER α基因6个不同位点（密码子10 T -> C、密码子87 G -> C、密码子243 C -> T、密码子325 C -> G、密码子594 G -> A和内含子1 C -> G）的基因型分布，并确定了它们与子宫内膜癌的相关性。应用序列特异性聚合酶链反应（PCR）技术对113例子宫内膜癌组织进行了DNA分型。以200名健康对照者为对照，计算变异基因型的相对危险度。与对照组相比，子宫内膜癌患者第10位密码子的变异基因型频率显著降低。9例H3子宫内膜癌患者（8.0%）显示10 C/C基因型，而200例健康对照者中有27例（13.5%）显示10 C/C基因型。与野生型相比，基因型10 C/C的相对风险计算为0.44。113例子宫内膜癌患者中有45例（39.8%）在密码子10上显示T/C基因型，而200名健康对照者中有111例（55.5%）显示II I基因型。与野生型相比，10 T/C基因型的相对危险度为0.67。在子宫内膜癌患者和健康对照组中均未检测到第87位密码子的多态性。其他基因座，内含子1和密码子243，325和594，没有显示出与子宫内膜癌的相关性。与对照组相比，子宫内膜癌患者中密码子10上的等位基因频率也显著降低。子宫内膜癌患者226个等位基因中有63个（27.9%）显示等位基因C，而健康对照组400个中有165个（41.2%）显示等位基因C。与野生型相比，等位基因10 C的相对风险计算为0.67。其他基因座，内含子1和密码子243，325和594，没有显示癌症患者和对照组之间的差异。所有基因型和等位基因分布符合Hardy-Weinberg平衡。本研究首次证明了10 C等位基因对子宫内膜癌的保护作用。因此，ER α的遗传性改变可能与雌激素代谢的变化有关，从而可能解释子宫内膜癌发病率的个体间差异。(C)2002 Elsevier Science（美国）。All rights reserved.
It is hypothesized that polymorphisms of estrogen receptor-alpha (ERalpha) gene are involved in endometrial cancer. To test this hypothesis, the genotype distributions of six different loci (codon 10 T --> C, codon 87 G --> C, codon 243 C --> T, codon 325 C --> G, codon 594 G --> A, and intron 1 C --> G) of the ERalpha gene were investigated and their association with endometrial cancer was determined. The DNA from 113 cases of human endometrial cancer was analyzed by sequence-specific polymerase chain reaction. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The frequency of variant genotype on codon 10 was significantly lower in endometrial cancer patients as compared to controls. Nine of H 3 endometrial cancer patients (8.0%) showed genotype 10C/C compared to 27 of 200 healthy controls (13.5%). The relative risk of genotype 10C/C was calculated as 0.44, compared to wild-type. Forty-five of 113 endometrial cancer patients (39.8%) showed genotype T/C on codon 10 compared to I I I of 200 healthy controls (55.5%). The relative risk of genotype 10T/C was calculated as 0.67, compared to wild-type. The polymorphism on codon 87 was not detected both in endometrial cancer patients and in healthy control. Other loci, intron 1, and codons 243, 325, and 594, did not show a correlation with endometrial cancer. The frequency of alleles on codon 10 was also significantly lower in endometrial cancer patients as compared to controls. Sixty-three of 226 alleles (27.9%) of endometrial cancer patients showed allele C compared to 165 of 400 (41.2%) of healthy controls. The relative risk of allele 10C was calculated as 0.67, compared to wild-type. Other loci, intron 1, and codons 243, 325, and 594, did not show a difference between cancer patients and controls. All genotype and allelic distributions were in accordance with the Hardy-Weinberg equilibrium. The present study demonstrates for the first time a protective effect of 10C allele against endometrial cancer. Thus, inherited alterations in ERalpha may be associated with changes in estrogen metabolism and thereby may possibly explain inter-individual differences in disease incidences of endometrial cancer. (C) 2002 Elsevier Science (USA). All rights reserved.