Yoon Hyung-Suk, Zheng Wei, Cai Hui, Wu Jie, Shidal Chris, Wang Jifeng, Shu Xiao-Ou, Waterboer Tim, Blot William J, Cai Qiuyin
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
Division of Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DFKZ), Heidelberg, Germany.
Cancer Epidemiol. 2022 Dec;81:102288. doi: 10.1016/j.canep.2022.102288. Epub 2022 Nov 1.
Mutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking.
In this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies.
After adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10-8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24-6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30-16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33-13.89).
Our findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.
TP53基因突变会导致产生针对p53（一种主要的肿瘤抑制蛋白）的自身抗体。尽管研究表明p53自身抗体与人类癌症有关，但关于肺癌的流行病学证据仍然缺乏。
在南方社区队列研究中进行的这项巢式病例对照研究中，我们调查了循环p53自身抗体与随后患肺癌风险之间的关联。使用从295例病例及其个体匹配对照在任何癌症诊断之前采集的血样，通过基于荧光微球的多重血清学评估对p53的血清反应性。使用条件逻辑回归模型估计与p53自身抗体相关的肺癌风险的比值比（OR）和95%置信区间（CI）。
在调整潜在混杂因素后，p53血清阳性与非裔美国人患肺癌风险增加显著相关（OR=2.98，95%CI：1.10-8.06），但在欧裔美国人中无此关联（OR=1.21，95%CI：0.24-6.15）。阳性关联仅限于男性（OR=4.59，95%CI：1.30-16.16）以及从采血到诊断间隔时间较短（≤4年）的参与者（OR=4.30，95%CI：1.33-13.89）。
我们的研究结果进一步证明了p53自身抗体可作为肺癌的生物标志物。
