Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2012 Jan 15;118(2):485-92. doi: 10.1002/cncr.26222. Epub 2011 Jun 29.
Because of the structural and biochemical similarities between the antitumor p53 and p73 proteins, the authors hypothesized that individuals who carry high-risk genotypes of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms have a higher risk of developing second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN).
A cohort of 1269 patients with index cases of SCCHN was recruited between May 1995 and January 2007 at The University of Texas MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms. A log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk among different risk groups with the combined risk genotypes of the 2 polymorphisms.
The data demonstrated that patients with p53 WP + PP and p73 GC/GC genotypes had a worse SPM-free survival and an increased SPM risk compared with the corresponding p53 WW and p73 GC/AT + AT/AT genotypes. After combining the 2 polymorphisms, a borderline significantly or significantly reduced SPM-free survival and increased SPM risk were observed in the medium-risk group (p53 WW and p73 GC/GC or p53 P carriers and p73 AT carriers) and high-risk group (p53 P carriers and p73 GC/GC) compared with low-risk group (p53 WW and p73 AT carriers), respectively.
The results suggest an increased risk of SPM after index SCCHN with both p53 and p73 polymorphisms individually and in combination.
由于抗肿瘤 p53 和 p73 蛋白在结构和生化上具有相似性，作者假设携带 p53 密码子 72 高风险基因型和 p73 G4C14-to-A4T14 多态性的个体，在发生头颈部鳞状细胞癌（SCCHN）后，发生第二原发恶性肿瘤（SPM）的风险更高。
1995 年 5 月至 2007 年 1 月，在德克萨斯大学 MD 安德森癌症中心招募了 1269 名头颈部鳞状细胞癌患者，对他们进行了随访以观察 SPM 的发生。对患者的 p53 密码子 72 和 p73 G4C14-to-A4T14 多态性进行了基因分型。采用对数秩检验和 Cox 比例风险模型比较了不同风险组的 SPM 无进展生存率和 SPM 风险，比较了这两种多态性的联合风险基因型。
数据表明，与 p53 WW 和 p73 GC/AT+AT/AT 基因型相比，p53 WP+PP 和 p73 GC/GC 基因型的患者 SPM 无进展生存率更差，SPM 风险更高。将两种多态性结合后，中危组（p53 WW 和 p73 GC/GC 或 p53 P 携带者和 p73 AT 携带者）和高危组（p53 P 携带者和 p73 GC/GC）与低危组（p53 WW 和 p73 AT 携带者）相比，SPM 无进展生存率有边缘显著或显著降低，SPM 风险显著增加。
这些结果表明，p53 和 p73 多态性单独和联合存在时，会增加头颈部鳞状细胞癌后 SPM 的风险。
