CICS-UBI-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interio, Avenida Infante D. Henrique, 6200-506, Covilhã, Portugal.
Mol Biol Rep. 2013 Aug;40(8):5093-103. doi: 10.1007/s11033-013-2611-6. Epub 2013 May 12.
Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between -397 PvuII (T>C) and -351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case-control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR-RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95% CI 0.070-0.456; P<0.001) or heterozigozity (OR 0.223; 95% CI 0.089-0.561; P=0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95% CI 0.049-1.035; P=0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95% CI 0.194-0.843; P=0.014), compared with PX (PPXX+PPXx+PpXX+PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D=0.044, r2=0.049, X2=5.216, P=0.022) and controls (D=0.090, r2=0.139, X2=16.819, P<0.001), but not in the entire sample population analyzed as a whole (D=0.087, r2=0.0076, X2=1.733, P=0.188). In conclusion, in this case-control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.
雌激素受体 alpha（ERα）介导雌激素在雌激素敏感组织如乳房中的生物学效应，其存在遗传多态性。为了评估雌激素受体α基因内含子 1 中的-397 PvuII（T>C）和-351 XbaI（A>G）限制性片段长度多态性（RFLPs）与乳腺癌易感性之间的关系，我们在 BRCA1 185delAG 和 5382insC/BRCA2 6174delT 阴性的葡萄牙女性中进行了病例对照研究。研究人群由 107 名经组织学诊断为乳腺癌的患者和 121 名无乳腺癌病史的女性组成。从血液样本中提取基因组 DNA，并通过 PCR-RFLP 进行基因分型分析。XbaI 多态性与 X 等位基因纯合子（OR 0.178；95%CI 0.070-0.456；P<0.001）或杂合子（OR 0.223；95%CI 0.089-0.561；P=0.001）携带者的乳腺癌发生风险显著降低相关。PvuII 多态性与风险降低无显著相关性。PvuII 和 XbaI 多态性的联合分析显示，两种基因型之间没有协同作用，除了同时携带 pp 和 xx 基因型的个体，其乳腺癌发生风险降低（OR 0.226；95%CI 0.049-1.035；P=0.044）。将 PvuII 和 XbaI 基因型组合成单倍型显示，携带两个 px（ppxx）单倍型的个体乳腺癌发生风险降低（OR 0.405；95%CI 0.194-0.843；P=0.014），与 PX（PPXX+PPXx+PpXX+PpXx）单倍型相比。病例和对照组中 PvuII 和 XbaI 多态性均处于连锁不平衡状态（病例：D=0.044，r2=0.049，X2=5.216，P=0.022；对照组：D=0.090，r2=0.139，X2=16.819，P<0.001），但在整个样本人群中未处于连锁不平衡状态（D=0.087，r2=0.0076，X2=1.733，P=0.188）。总之，在这项病例对照研究中，我们发现 ERα 基因 XbaI 多态性可能会改变该人群中个体对乳腺癌的易感性。
