Department of Oncology, Chinese PLA General Hospital, Beijing, China.
DNA Cell Biol. 2012 Feb;31(2):230-7. doi: 10.1089/dna.2011.1305. Epub 2011 Oct 19.
The TP53 homolog p73 is structurally and functionally similar to TP53 and plays an important role in modulating cell-cycle control, apoptosis, and cell growth. G4C14-to-A4T14 is the most commonly studied polymorphism of this gene for its association with risk of cancers, but the results are confusing rather than conclusive. We performed a meta-analysis using 21 eligible studies with a total of 7581 patients and 10,413 controls to summarize the data for an association between the p73 G4C14-to-A4T14 polymorphism and cancer risk. Compared with the common GC/GC genotype, the AT carriers (AT/GC, AT/AT) had a 1.18-fold elevated risk of cancer (95% confidence interval [CI]=1.11-1.25, p<0.00001) in a dominant genetic model as estimated in a fixed effect model. The effect of the G4C14-to-A4T14 polymorphism was further evaluated through stratification analysis. In four lung cancer studies, the variant genotypes had a significantly increased risk of lung cancer (odds ratio [OR]=1.16, 95% CI=1.04-1.28, p=0.005). Similar phenomena were also found in two squamous cell carcinoma of the head and neck studies (OR=1.32, 95% CI=1.12-1.56, p=0.0010), two oral cancer studies (OR=1.57, 95% CI=1.26-1.95, p<0.0001), and three colorectal cancer studies (OR=1.23, 95% CI=1.01-1.50, p=0.04). Increased risk of cancer associated with G4C14-to-A4T14 variant genotypes was pronounced in Caucasians (OR=1.21, 95% CI=1.11-1.31, p<0.00001), the Japanese population (OR=1.24, 95% CI=1.01-1.52, p=0.04), and the Korean population (OR=1.27, 95% CI=1.07-1.52, p=0.007). Our meta-analysis suggests that the p73 G4C14-to-A4T14 polymorphism genotypes (GC/AT+AT/AT) may be associated with an increased risk of cancer in most cancer types and ethnicities.
TP53 同源物 p73 在结构和功能上与 TP53 相似，在调节细胞周期控制、细胞凋亡和细胞生长方面发挥着重要作用。G4C14 到 A4T14 是该基因最常研究的多态性，因为它与癌症风险有关，但结果令人困惑而不是结论性的。我们进行了一项荟萃分析，使用了 21 项符合条件的研究，共有 7581 名患者和 10413 名对照者，总结了 p73 G4C14 到 A4T14 多态性与癌症风险之间的关联数据。与常见的 GC/GC 基因型相比，在固定效应模型中，在显性遗传模型中，AT 携带者（AT/GC、AT/AT）患癌症的风险增加了 1.18 倍（95%置信区间[CI]为 1.11-1.25，p<0.00001）。通过分层分析进一步评估了 G4C14 到 A4T14 多态性的影响。在四项肺癌研究中，变异基因型患肺癌的风险显著增加（比值比[OR]=1.16，95%CI=1.04-1.28，p=0.005）。在两项头颈部鳞状细胞癌研究、两项口腔癌研究和三项结直肠癌研究中也发现了类似的现象（OR=1.32，95%CI=1.12-1.56，p=0.0010；OR=1.57，95%CI=1.26-1.95，p<0.0001；OR=1.23，95%CI=1.01-1.50，p=0.04）。与 G4C14 到 A4T14 变异基因型相关的癌症风险增加在高加索人群中更为明显（OR=1.21，95%CI=1.11-1.31，p<0.00001）、日本人群（OR=1.24，95%CI=1.01-1.52，p=0.04）和韩国人群（OR=1.27，95%CI=1.07-1.52，p=0.007）。我们的荟萃分析表明，p73 G4C14 到 A4T14 多态性基因型（GC/AT+AT/AT）可能与大多数癌症类型和种族的癌症风险增加有关。
