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Genetic variants in p53-related genes confer susceptibility to second primary malignancy in patients with index squamous cell carcinoma of head and neck

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机构： [1]Department of Head & Neck Surgery, The University of Texas MD AndersonCancer Center, Houston, TX, USA, [2]Department of Stomatology, JinlingHospital, School of Medicine, Southern Medical University, Nanjing, China, [3]Department of Epidemiology, The University of Texas MD Anderson CancerCenter, Houston, TX, USA, [4]Department of Otolaryngology-Head and NeckSurgery, Beijing Tongren Hospital, Capital Medical University, Beijing,China, [5]Division of Biostatistics and Human Genetics Center, Universityof Texas School of Public Health, Houston, TX, USA, [6]Department ofRadiology, East Hospital, Tongji University School of Medicine, Shanghai,China [7]Department of Otorhinolaryngology and Head & Neck Surgery,Yuhuangding Hospital of Qingdao University, Yantai, China

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Because of their important roles in mediating the stabilization and expression of p53, we hypothesized that high-risk genotypes of polymorphisms in p53-related genes, including p53, p73, p14(ARF), MDM2 and MDM4, may be associated with an increased risk of second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). We analyzed data from a cohort of 1283 patients with index SCCHN who were recruited between 1995 and 2007 at MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for nine polymorphisms of p53-related genes. A log-rank test and Cox models were used to compare SPM-free survival and risk. Our results demonstrated that each p53-related polymorphism had a moderate effect on increased SPM risk, but when we combined risk genotypes of these nine polymorphisms together, we found that SPM-free survival was significantly shorter among risk groups with a greater number of combined risk genotypes. SPM risk increased with increasing number of risk genotypes (P < 0.0001 for trend). Compared with the low-risk group (03 combined risk genotypes), both the medium-risk (45 combined risk genotypes) and high-risk (69 combined risk genotypes) groups had significantly increased SPM risk [hazard ratio (HR): 1.6; 95% confidence interval (CI): 1.02.6 and HR: 3.0; 95% CI: 1.85.0, respectively]. Moreover, such significant associations were even higher in several subgroups. Our findings suggest that combined risk genotypes of p53-related genes may jointly modify SPM risk, especially in patients who are smokers and those with index non-oropharyngeal cancers. However, larger studies are needed to validate our findings.

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出版当年[2012]版：

大类 | 2 区医学

小类 | 2 区肿瘤学

最新[2025]版：

大类 | 3 区医学

小类 | 4 区肿瘤学

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出版当年[2011]版：

Q1 ONCOLOGY

最新[2024]版：

Q2 ONCOLOGY

影响因子： 2.9 最新[2024版] 3.4 最新五年平均 5.702 出版当年[2011版] 5.203 出版当年五年平均 5.402 出版前一年[2010版] 5.635 出版后一年[2012版]

第一作者：

第一作者机构： [1]Department of Head & Neck Surgery, The University of Texas MD AndersonCancer Center, Houston, TX, USA, [2]Department of Stomatology, JinlingHospital, School of Medicine, Southern Medical University, Nanjing, China,

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通讯作者：

通讯机构： [1]Department of Head & Neck Surgery, The University of Texas MD AndersonCancer Center, Houston, TX, USA, [3]Department of Epidemiology, The University of Texas MD Anderson CancerCenter, Houston, TX, USA, [7]Department of Otorhinolaryngology and Head & Neck Surgery,Yuhuangding Hospital of Qingdao University, Yantai, China [*1]Department of Head & Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

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