Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)
Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)
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p53 和 MDM2 多态性与人乳头瘤病毒 (HPV) 相关食管鳞状细胞癌 (ESCC) 风险的关联
DOI：
10.1016/j.canep.2013.06.001
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发表时间：
2013-10-01
影响因子：
2.6
通讯作者：
Yuan, Xianglin
中科院分区：
文献类型：
--
作者：
Yang, Ju;Liu, Bo;Yuan, Xianglin
目的：尽管肿瘤抑制基因p53的多态性在许多肿瘤中已经被广泛研究，特别是与人乳头瘤病毒（HPV）感染相关的肿瘤。然而，结果仍然存在争议。我们以前的研究表明，HPV血清状态不是非吸烟者和非饮酒者食管鳞状细胞癌（ESCC）的独立危险因素。鉴于p53和HPV E6以及MDM 2癌蛋白在p53降解中的作用，我们验证了p53和MDM 2多态性与ESCC风险分层HPV 16 sero-status.Methods：307例ESCC患者和311例健康对照者的p53 Arg 72 Pro（rs 1042522）和MDM 2（rs 937283）的单核苷酸多态性进行基因分型。采用酶联免疫吸附试验检测血清中HPV 16的存在与否。采用多变量logistic回归分析评估p53和MDM 2多态性与按HPV 16血清状态分层的ESCC风险的可能关联。携带p53 Arg/Arg或Arg/Pro的患者发生食管鳞癌的风险较高（P < 0.001，比值比[OR] 4.98，95%可信区间[CI] 3.46-7.17），然而，在MDM 2 rs 937283中未发现。在携带p53 Arg/Arg或Arg/Pro和HPV 16血清阳性的患者中，食管SCC的风险显著增加（P < 0.001，OR 9.33，95%CI 5.44-16.0），但MDM 2 rs 937283的风险不显著。携带Arg/Arg或Arg/Pro和HPV 16血清阳性的吸烟者食管癌的风险进一步升高（P < 0.001，OR 27.05，95%CI 11.06-66.16）或饮酒者结论：HPV 16阳性与p53 Arg/Arg或Arg/Pro阳性协同作用，增加食管鳞癌的发病风险，尤其是吸烟者和饮酒者。(C)2013爱思唯尔有限公司保留所有权利。
Purpose: Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.Methods: Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.Results: Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P < 0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46-7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P < 0.001, OR 9.33, 95% CI 5.44-16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P < 0.001, OR 27.05, 95% CI 11.06-66.16) or drinkers (P < 0.001, OR 13.20, 95% CI 5.74-30.38).Conclusion: HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers. (C) 2013 Elsevier Ltd. All rights reserved.