Franeková M, Zúbor P, Stanclová A, Dussan C A, Bohusová T, Galo S, Dobrota D, Kajo K, Péc M, Racay P
Department of Biology, Comenius University in Bratislava, Martin, Slovak Republic.
Neoplasma. 2007;54(2):155-61.
Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. As a transcription factor p53 controls many cell processes and helps in prevention of cancer development. The p53 gene is polymorphic. Polymorphisms can affect the important regions involved in protein tumor suppressor activity. The well-known polymorphisms are the polymorphisms BstUI in exon 4 and MspI in intron 6. Both are supposed to be associated with cancer development. The purpose of this study was to investigate the genotype frequencies and associations of these polymorphisms with breast cancer in Slovak population. We observed the prevalence of BstUIPro (27.47%) and MspIA1 (17.58%) alleles and BstUIPro/Pro (8.79%) and MspIA1/A1 (5.49%) genotypes in breast cancer patients in comparison with controls 23.40%, 14.10%, 5.77%, 1.92% respectively. However the differences were not significant. After division of the cases and controls according to the age the prevalence of the risk alleles and genotypes in women at the age 50 years or less was higher as compared to women older than 50 years. In the younger women group, the p53 BstUI polymorphism genotype frequencies were 6.2% for BstUIPro/Pro, 31.0% for BstUIArg/Pro and 62.8% for BstUIArg/Arg in controls and 11.11 %, 40.74% and 48.15% in cases respectively. The risk of disease for BstUIPro/Pro genotype was more than two-fold higher in comparison with the BstUIArg/Arg (OR=2.34, 95% CI=0.53-10.24). In p53 MspI the genotype frequencies were 1.77% for MspIA1/A1, 24.78% for MspIA1/A2 and 73.45% for MspIA2/A2 in controls and 11.11%, 18.52% and 70.37% in cases respectively. The risk of disease for MspIA1/A1 genotype was more than six-fold higher in comparison with the MspIA2/A2 (OR=6.55, 95% CI=1.02-41.98). When we evaluated the association of both polymorphisms together with the breast cancer risk we observed that the highest risk was connected with the genotype BstUIPro/Pro / MspIA1/A1 (OR=2.99, 95% CI=0.69-13.06). Our results indicate that both BstUI and MspI p53 polymormphisms might play the role in the breast cancer development especially in women younger than 50 years.
蛋白质p53是参与细胞周期调控和细胞凋亡的肿瘤抑制因子。作为一种转录因子，p53控制着许多细胞过程，并有助于预防癌症的发生。p53基因具有多态性。多态性可影响参与蛋白质肿瘤抑制活性的重要区域。著名的多态性是外显子4中的BstUI多态性和内含子6中的MspI多态性。两者都被认为与癌症的发生有关。本研究的目的是调查斯洛伐克人群中这些多态性的基因型频率及其与乳腺癌的关联。我们观察了乳腺癌患者中BstUIPro（27.47%）和MspIA1（17.58%）等位基因以及BstUIPro/Pro（8.79%）和MspIA1/A1（5.49%）基因型的患病率，与之相比，对照组分别为23.40%、14.10%、5.77%、1.92%。然而，差异并不显著。根据年龄对病例和对照进行划分后，50岁及以下女性中风险等位基因和基因型的患病率高于50岁以上的女性。在年轻女性组中，对照组中BstUIPro/Pro基因型频率为6.2%，BstUIArg/Pro为31.0%，BstUIArg/Arg为62.8%，病例组中分别为11.11%、40.74%和48.15%。与BstUIArg/Arg相比，BstUIPro/Pro基因型的疾病风险高出两倍多（OR=2.34，95%CI=0.53-10.24）。在p53 MspI中，对照组中MspIA1/A1基因型频率为1.77%，MspIA1/A2为24.78%，MspIA2/A2为73.45%，病例组中分别为11.11%、18.52%和70.37%。与MspIA2/A2相比，MspIA1/A1基因型的疾病风险高出六倍多（OR=6.55，95%CI=1.02-41.98）。当我们评估这两种多态性与乳腺癌风险的关联时，我们观察到最高风险与基因型BstUIPro/Pro / MspIA1/A1相关（OR=2.99，95%CI=0.69-13.06）。我们的结果表明，BstUI和MspI p53多态性可能在乳腺癌的发生中起作用，尤其是在50岁以下的女性中。
