Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
Gene. 2012 Sep 15;506(2):295-7. doi: 10.1016/j.gene.2012.07.007. Epub 2012 Jul 16.
P53 plays a critical role in the maintenance of genomic stability as well as the control of cell growth and apoptosis. Recently, an uncommon P53 genetic variant (rs78378222) was reported to be significantly associated with multiple cancers in Caucasians in a genome-wide association study. rs78378222 locates in the 3'-untranslated region of the P53 gene, and this A-to-C polymorphism results in changes of the AATAAA polyadenylation signal to AATACA, which leads to impaired 3'-end processing of P53 mRNA and decreased P53 expression.
We evaluated the association between this polymorphism and esophageal squamous cell carcinoma (ESCC) risk in a case-control cohort consisting of 405 ESCC patients and 810 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression.
We did observe this polymorphism with low minor allele frequency in Chinese Han population. Additionally, significantly increased ESCC risk was associated with P53 rs78378222 A>C polymorphism. Compared with rs78378222AA carriers, the OR of developing ESCC for AC carriers was 3.22 (95% CI=1.71-6.33, P=1.34×10(-4)).
These results suggest that this functional uncommon P53 rs78378222 variant is associated with ESCC risk in the current Han Chinese population.
P53 在维持基因组稳定性以及控制细胞生长和凋亡方面起着关键作用。最近，一项全基因组关联研究报告称，一种罕见的 P53 基因变异（rs78378222）与白种人中的多种癌症显著相关。rs78378222 位于 P53 基因的 3'-非翻译区，这种 A 到 C 的多态性导致 AATAAA 多聚腺苷酸化信号变为 AATACA，从而导致 P53 mRNA 的 3'-末端加工受损和 P53 表达降低。
我们在一个由 405 名 ESCC 患者和 810 名健康对照组成的病例对照队列中评估了该多态性与食管鳞状细胞癌（ESCC）风险之间的关联。通过逻辑回归计算比值比（OR）和 95%置信区间（CI）。
我们确实在汉族人群中观察到这种多态性的等位基因频率较低。此外，P53 rs78378222 A>C 多态性与 ESCC 风险显著增加相关。与 rs78378222AA 携带者相比，AC 携带者发生 ESCC 的 OR 为 3.22（95%CI=1.71-6.33，P=1.34×10(-4)）。
这些结果表明，这种功能性罕见的 P53 rs78378222 变体与当前汉族人群的 ESCC 风险相关。
