Ignaszak-Szczepaniak Magdalena, Horst-Sikorska Wanda, Sawicka Joanna, Kaczmarek Marta, Slomski Ryszard
Family Medicine Department, Karol Marcinkowski University of Medical Sciences 60-355 Poznan, Poland.
Oncol Rep. 2006 Jul;16(1):65-71.
The TP53 polymorphism occurs at codon 72 of exon 4 with two alleles encoding either arginine or proline. The association between this common polymorphism and risk of different cancers has been extensive studied, however various reports are controversial. We have analyzed the 72Pro polymorphic variant in patients with adrenocortical tumors to evaluate whether 72G--> C substitution at codon 72 of TP53 gene may be associated with increased risk for malignancy in adrenal cortex in comparison to the control group. DNA extracted from peripheral leucocytes of 46 Polish patients with adrenocortical tumors (17 malignant and 29 benign) and 50 controls was examined by PCR-HD method followed by direct sequencing. TP53 polymorphism in codon 72 was found in 47% of ACC cases, in 28% of patients with adenomas and in 24% of controls. The genotype Arg/Arg, Arg/Pro and Pro/Pro distribution was respectively 53%/35%/12% for cancers, 72%/28%/0% for benign tumors and 76%/24%/0% for controls. High frequency of 72Pro allele in patients with carcinoma (29%) in comparison to the benign tumors (14%) and controls (12%) was statistically analyzed. We found that 72Pro variant of TP53 gene was associated with a significantly increased risk of ACC (OR = 3.05; 95% CI = 1.17-7.91, p=0.03). Our results suggest that the TP53 codon 72 polymorphism could be associated with susceptibility for adrenocortical cancer in the examined Polish patients.
TP53基因多态性发生在第4外显子的第72密码子,有两个等位基因,分别编码精氨酸或脯氨酸。这种常见多态性与不同癌症风险之间的关联已得到广泛研究,但各种报告存在争议。我们分析了肾上腺皮质肿瘤患者的72Pro多态性变体,以评估TP53基因第72密码子的72G→C替换与对照组相比,是否可能增加肾上腺皮质恶性肿瘤的风险。采用PCR-HD方法并直接测序,检测了46例波兰肾上腺皮质肿瘤患者(17例恶性和29例良性)外周血白细胞和50例对照者提取的DNA。在47%的肾上腺皮质癌(ACC)病例、28%的腺瘤患者和24%的对照者中发现了第72密码子的TP53多态性。Arg/Arg、Arg/Pro和Pro/Pro基因型分布在癌症患者中分别为53%/35%/12%,良性肿瘤患者中为72%/28%/0%,对照者中为76%/24%/0%。对癌患者(29%)与良性肿瘤患者(14%)和对照者(12%)相比72Pro等位基因的高频率进行了统计学分析。我们发现TP53基因的72Pro变体与ACC风险显著增加相关(OR = 3.05;95% CI = 1.17 - 7.91,p = 0.03)。我们的结果表明,在所检测的波兰患者中,TP53第72密码子多态性可能与肾上腺皮质癌易感性相关。