湖北地区汉族人群p53基因第72位密码子多态性与宫颈鳞癌相关性

[目的]探讨p53基因第72位密码子多态性与湖北地区汉族人群宫颈癌相关性。[方法]采用PCR法检测104例宫颈鳞癌及84例正常宫颈组织标本中p53基因第72位密码子的基因型。[结果]p53基因第12位密码子的3种基因型Arg/Arg、Arg/Pro、Pro/Pro在宫颈鳞癌组比例分别为38.5%、44.2%和17.3%;对照组中分别为52.4%、40.5%和7.1%。Pro/Pro基因型在宫颈鳞癌组中所占比例显著高于正常宫颈组织(P=0.018)。[结论]p53基因第72位密码子Pro/Pro基因型是湖北地区汉族女性发生宫颈鳞癌的遗传易感因素之一。     

晚期非小细胞肺癌对铂类药物的化疗敏感性与p53和p73基因多态的关系

目的探讨细胞凋亡相关基因p53和p73的遗传多态,与晚期非小细胞肺癌（NSCLC）对铂类药物化疗敏感性的关系。方法以聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）和突变扩增阻抑系统（ARMS）分析方法,对165例以顺铂（DDP）或卡铂（CBP）为主进行化疗的晚期NSCLC患者,进行p53第72密码子Arg→Pro多态,和p73第2外显子G4C14-A4T14多态的检测,2～3个疗程后进行效果评价。以非条件Logistic回归模型比较不同基因型与化疗疗效的关系。结果携带p53 72Pro等位基因患者的化疗敏感性,是携带p53 72Arg／Arg基因型患者的2、46倍（95％CI,1．11～5．45,P=0．026）;而携带至少1个p73突变等位基因（A4T14）的患者,其化疗敏感性是携带p73 G4C14／G4C14基因型患者的2．22倍（95％讲,1．14～4、30,P=0．019）。2个多态位点合并分析结果显示,同时携带p53和p73野生基因型的患者,化疗有效率为7．7％;而携带1个、2个和≥3个p53和p73变异等位基因的患者,化疗有效率分别为34．8％、42．2％和40、7％。结论p53和p73基因遗传多态与晚期NSCLC患者对以铂类药物为主的化疗敏感性有关。     

p53基因codon 72多态性与乳腺癌术后放化疗疗效相关性分析

目的:分析p53基因codon 72多态性与乳腺癌患者术后放化疗的预后相关性。方法:选取北京大学肿瘤医院乳腺癌患者术后接受放化疗427 例,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）方法分析其p53基因codon 72多态性,比较不同基因型患者间复发及生存的差异。结果:全部患者基因型分布为Pro/Pro 型18.3%（78/427）、Pro/Arg型44.0%（188/427）、Arg/Arg型37.7%（161/427）。3 种基因型间无局部复发生存（LRFS）、无局部区域复发生存（LRRFS ）、无远处转移生存（DDFS）及总生存（OS）均无显著性差异（均P>0.05）。 427 例患者中雌激素受体（ER）阳性为303 例,其中Arg/Arg基因型患者OS明显优于Pro/Pro 基因型患者（χ2=6.330,P=0.042）。 在多因素分析中p53基因codon 72多态性是ER阳性患者LRFS、LRRFS 、DDFS及OS的独立预后因素,Pro/Pro 基因型的患者较Arg/Arg基因型的局部复发风险增加5.9 倍（HR= 5.9,95%CI 1.1～31.1,P=0.036）,局部区域复发风险增加3.1 倍（HR= 3.1,95%CI 1.1～9.1,P=0.039）,远处转移风险增加2.8 倍（HR= 2.8,95%CI 1.3～6.0,P=0.010）,死亡风险增加4 倍（HR= 4.0,95%CI 1.3～12.0,P=0.013）。 结论:在ER阳性的乳腺癌术后接受放化疗患者中,Pro/Pro 基因型的局部及局部区域复发风险、远处转移风险、死亡风险均高于Arg/Arg基因型。      

p53基因多态性与宫颈癌关系的初步研究

背景与目的:p53基因多态性可影响人乳头状瘤病毒(human papillo-mavirus,HPV)介导的p53降解.本研究的目的是观察p53基因多态性在广东妇女中的分布情况及了解不同p53基因型对宫颈癌发生的影响.方法:收集2002年9月～2003年5月在中山大学肿瘤防治中心妇科治疗的宫颈癌患者46例(病例组)及妇科良性肿瘤患者84例(对照组)的宫颈涂片,用PCR对由涂片中提取的DNA进行HPV DNA检测及p53多态性检测.结果:HPV DNA阳性率在病例组和对照组中分别为47.8%和20.2%.在病例组中,Arg/Arg、Pro/Pro和Arg/Pro基因型分别占56.5%、21.7%和21.7%;在对照组中,Arg/Arg、Pro/Pro和Arg/Pro基因型分别占71.4%、20.2%和8.3%.Arg/Arg(OR,0.520;95%CI,0.245～1.102)和Arg/Pro基因型(OR,1.095;95%CI,0.454～2.639)在病例组和对照组之间无显著性差异;而Pro/Pro基因型在两组之间有显著性差异(OR,3.056;95%CI,1.076～8.678),但在HPV阳性妇女中,这种基因型分布的无显著性差异.结论:Arg/Arg基因型可能不是宫颈癌的高危因素,而Pro/Pro基因型患者可能易患宫颈癌.     

p53Arg72Pro多态性与HPV相关宫颈癌发生机制

[目的]探讨p53Arg72Pro多态性与HPV相关宫颈癌发生机制的关系。[方法]采用PCR技术检测210例宫颈癌和95例正常宫颈组织的HPV16DNA．采用免疫组化方法及TUNEL检测p53Arg72Pro三种基因型中p53、p21、Bax、Ki-67蛋白（P1）表达以及细胞凋亡（AI）。[结果]宫颈癌HPV16阳性率为70．5％,与正常宫颈组织（7．4％）相比差异具有统计学意义（P〈0．05）。HPV16阳性的宫颈癌中：①p53蛋白阴性和弱阳性表达率（73．6％）高于强阳性率（26．4％）,其中p53Arg的阴性表达率（39．2％）高于p53Pro（16．7％）,差异有统计学意义（P〈0．05）;②p21蛋白阴性和弱阳性组中,p53Pro型中PI高于p53Arg型,差异有统计学意义（P〈0．05）;④Bax蛋白阴性和弱阳性组中,p53Pro型中AI低于p53Arg型,差异有统计学意义（P〈0．05）。[结论]p53蛋白可被HPV16E6蛋白降解,其中p53Arg蛋白更易被降解;p53Arg和p53Pro蛋白被降解后,两者抑制细胞增殖能力的降低和诱导细胞凋亡能力的降低程度不同．其中p53Pro蛋白转录激活p21和Bax基因的功能及细胞周期阻滞作用的降低更明显。     

p53codon72单核苷酸多态性与肝细胞癌发病风险的关系

[目的]探讨广西地区p53基因codon72单核苷酸多态性(SNP)与肝细胞癌(HCC)发病风险的关系。[方法]采用TaqMan MGB探针等位基因分型技术对985例肝癌病例和相匹配的992例非肿瘤对照的p53 codon72(Arg>Pro,rs1042522)基因型进行检测,并分析该SNP与肝癌发病风险的关系。[结果]p53 codon72多态性与肝癌发病风险之间无统计学关联(Arg/Pro:校正OR=1.15,95%CI:0.83～1.59;Pro/Pro:校正OR=1.16,95%CI:0.80～1.68;Arg/Pro+Pro/Pro:校正OR=1.15,95%CI:0.85～1.57)。按是否吸烟、饮酒、HBV和HCV感染分层分析,亦未发现p53 codon72多态性与肝癌发病风险有关。但基因—环境交互作用显示,该基因多态性与吸烟、饮酒和HBV感染存在交互作用,OR值分别为2.42(95%CI:1.47～3.97)、2.96(95%CI:1.82～4.80)和62.74(95%CI:34.39～114.46)。[结论]p53codon72的单独效应可能与肝癌易感性无关联,但该SNP与吸烟、饮酒和HBV感染存在基因—环境交互作用,增加肝癌的发病风险。     

53BP1和p53基因多态性与食管鳞癌、贲门腺癌遗传易感性的关系

背景与目的:p53结合蛋白1(53BP1)可通过增强p53的转录活性,而在肿瘤抑制方面发挥重要作用.在53BP1的启动子区-885 bp处存在着T到G的单核苷酸多态性(single nucleotide polymorphism,SNP).本实验探讨53BP1T885G基因多态性以及p53 Arg72Pro的多态性与中国河北高发区人群食管鳞癌(esophageal squamous cell carcinoma,ESCC)和贲门腺癌(gastric cardiac adenocarcinoma,GCA)遗传易感性的关系.方法:应用引物引入限制性内切酶分析-聚合酶链反应(primer-introduced restriction analysis-polymerase chain reaction,PIRA-PCR)方法.分析624例患者(其中ESCC 349例,GCA 275例)和635例健康对照者的53BP1 T885G和p53 Arg72Pro的基因型.结果:53BP1 T885G基因型分布在总体ESCC、GEA病例组与健康对照组间差异无统计学意义(P＞0.05).根据吸烟状况和上消化道肿瘤(upper gastrointestinal cancer,UGIC)家族史分层分析显示,T885G基因型分布在病例组与健康对照组差异亦无统计学意义(P＞0.05).与Arg/Arg基因型相比,携带p53 Arg72Pro Pro/Pro基因型可降低总体GCA的发病风险,经性别、年龄、吸烟状况和UGIC家族史多因素校正后的OR值为0.79(95% CI=0.64～0.98);分层分析显示Pro/Pro基因型主要降低非吸烟组GCA的发病风险,校正后的OR值为0.72(95% CI=0.54～0.97).未发现p53Arg72Pro 对ESCC发病风险的影响.53BP1 T885G和p53 Arg72Pro 联合分析显示,在携带Pro等位基因(Arg/Pro Pro/Pro基因型)者中,同时携带T885G的G/G基因型可降低GCA的发病风险.校正后的OR值为0.74(95%CI=0.57～0.95).结论:53BP1 T885G位点可能与中国河北高发区ESCC、GCA的遗传易感性无关,p53 Arg72Pro的Pro/Pro 基因型可降低高发区GCA的发病风险.同时携带Pro等位基因(Arg/Pro Pro/Pro基因型)和53BP1 T885G的G/G基因型可降低高发区GCA的发病风险.     

中国人食管癌及肺癌发病风险与p53基因多态性

目的　比较中国北方人对食管癌及肺癌的易感性与p5 3基因第 72密码子多态性的关系。方法　应用序列特异性引物 ,以PCR方法检测 173例食管鳞状上皮癌、98例非小细胞肺癌患者及 136例健康对照者的p5 3基因第 72密码子的基因型。结果　食管癌与肺癌组p5 3等位基因及基因型分布无明显差异。食管癌和肺癌组的Pro等位基因频率明显高于对照组 (P值分别为 0 .0 2 4及0 .0 2 7)。Pro/Arg及Arg/Arg基因型频率在两肿瘤组及对照组差异无显著性 (P >0 .0 5 ) ,而食管癌和肺癌组的Pro/Pro基因型频率明显高于对照组 (P值分别为 0 .0 4 1及 0 .0 2 6 )。Pro纯合子患食管癌与肺癌的风险较Arg纯合子高 2倍左右 [校正比值比分别为 2 .12 (95 %CI=1.13～ 4 .0 1)和 2 .30 (95 %CI =1.13～ 4 .93) ],且与吸烟无协同作用。结论　Pro/Pro基因型为中国北方人患食管癌及肺癌的独立易感因素 ,两种肿瘤的发病可能有共同的遗传基础。     

p73基因多态性与乳腺癌遗传易感性的关系

  目的  探讨p73基因G4C14-A4T14多态性与中国重庆地区汉族女性乳腺癌遗传易感性的关系。  方法  采用病例对照研究, 利用Sequenom Mass Array?iPLEX GOLD系统对170例乳腺癌患者和178例健康者对照的p73基因G4C14-A4T14单核苷酸多态性进行了检测, 并对检测结果进行t检验、χ2检验和非条件Logistic回归分析。  结果  p73基因G4C14-A4T14多态基因型和等位基因型在乳腺癌组和对照组的分布频率差异无统计学意义(χ2=2.750, P=0.253;χ2=2.195, P=0.138);与携带GC/AT和AT/AT基因型的个体比较, 携带GC/GC基因型的个体患三阴性乳腺癌发病风险显著增加(OR=2.992, 95%CI: 1.300~6.890, P=0.010)。  结论  p73基因G4C14-A4T14多态性与中国重庆地区汉族女性三阴性乳腺癌的发病风险相关, GC/GC基因型是中国重庆地区汉族女性三阴性乳腺癌的易感基因型; 携带GC/GC基因型的乳腺癌可能预后不良。      

p53 condon72基因多态性与胃癌危险度关系--病例对照研究

目的 :探讨p53密码子 72基因多态性与胃癌危险度的关系 ,及其不同基因型与环境危险因素交互作用对胃癌发病的影响。方法 :在江苏省泰兴市进行以人群为基础的病例对照研究 ,胃癌病例 2 0 4例 ,对照 41 5例。结果 :病例中p53密码子 72的Pro Pro基因型的比例较对照中高 ,Pro Pro或Pro Arg两种基因型与Arg Arg比较OR为 1 50 (1 0 1～ 2 2 3)。p53基因还可与吸烟、饮酒、饮河水、嗜烫食等发生相乘或相加交互作用 ,影响胃癌发病。结论 :p53的Pro等位基因可能与胃癌危险度有关 ,并与其他环境危险因素交互作用 ,增加胃癌发病的危险。     

Association between a p73 Gene Polymorphism and Genetic Susceptibility to Non-small Cell Lung Cancer in the South of China

Background: This study aimed to identify any association between the p73 gene G4C14-to-A4T14 polymorphismand risk of non-small cell lung cancer (NSCLC) in the south of China. Materials and Methods: We genotypedthe p73 gene polymorphism of peripheral blood DNA from 168 patients with NSCLC and 195 normal controlsusing HRM (high resolution melting) and PCR-CTPP (polymerase chain reaction with confronting two-pairprimers). Results: The results of genotyping by HRM and PCR-CTPP were consistent with direct sequencing,the p73 genotype distribution in 168 lung cancer patients being as follows: GC/GC 101 cases (60.1%), GC/AT 59 cases (35.1%), AT/AT 8 cases (4.8%). The carriers of AT/AT genotype had a significantly reduced riskof NSCLC (OR=0.370; 95%CI: 0.170-0.806; p=0.010) as compared with non-carriers. However, we found norelations between p73 genotypes and histological type (p=0.798, x2=0.452), tumor stage (p=0.806, x2=0.806), orlymph node metastasis (p=0.578, x2=1.098). Conclusions: Our findings suggest that the p73 G4C14-to-A4T14polymorphism may be a modifier of NSCLC susceptibility in the Chinese population.     

Association of the p73 Gene G4C14-to-A4T14 Polymorphism with Increased Gastric Cancer Risk in a Northwestern Chinese Population

OBJECTIVE To evaluate the p73 gene G4C14-to-A4T14 double nucleotide polymorphism with both increased gastric cancer(GC) risk and different histological subtypes of GC in a northwestern Chinese population. METHODS Genotyping of the polymorphism of the p73 gene was conducted with PCR-CTPP. RESULTS All 385 GC patients including 305 diffuse-type and 80 intestinal-type cases and 412 healthy controls were investigated.The frequencies of p73 AT/AT,AT/GC,and GC/GC genotypes were 28.1%,47.1%,and 24.8% in the controls,and were 22.0%,45.0%,and 33.0% in GC cases respectively;the GC/GC homozygote frequency was higher in GC cases,mainly in diffuse type compared to the controls with OR=1.71(1.16～2.51) and 1.87 (95%CI,1.24～2.81) respectively.The results showed that carriers of the p73 G4A GC/GC homozygote had a 1.71-time higher risk of GC,especially of the diffuse-type GC compared to the controls. The carriers of the AT/GC heterozygote also had a slightly increased risk of GC cancer,mainly on intestinal-type GC.This is the first report that the p73 G4A double-nucleotide polymorphism is associated with an increased risk of diffuse-type gastric cancer. CONCLUTION The p73 G4A GC/GC genotype is associated with an increased risk of gastric cancer,especially of the GC diffuse-type.     

Association ofp53 codon arg72pro andp73 G4C14-to-A4T14 at exon 2 genetic polymorphisms with the risk of japanese breast cancer

BACKGROUND: The association between breast cancer risk and genetic polymorphisms of p53 at codon 72 (Arg72Pro) has been investigated by several studies, but the results are not consistent. The aim of this case-control study conducted in Nagoya, Japan, was to reconfirm the results of prior studies of polymorphisms of p53 Arg72Pro, and to test if polymorphisms of p73 G4C14-to-A4T14 at exon 2 (G4A) were also associated with breast cancer risk. METHODS: The cases were 200 breast cancer patients who visited Aichi Cancer Center Hospital. The controls were 282 local citizens who underwent a health check-up. All cases and controls were recruited from Chubu Japan. Genotyping was carried out by polymerase chain reaction with confronting two-pair primers. RESULTS: The p53 genotype distribution was 40.4% for Arg72 homozygous, 48.9% for heterozygous, and 10.7% for Pro72 homozygous in controls, and 32.0%, 50.0%, and 18.0% in cases, respectively. A comparison between cases and controls indicated a significantly increased risk for Pro72 homozygosity in cases (odds ratio=2.14; 95% confidence interval=1.21-3.79). The genotypic frequencies for p73 G4A were 54.3% for G/G, 39.7% for G/A, and 6.0% for A/A in controls; and 59.0%, 32.0%, and 9.0% in cases, respectively. There were no significant differences in p73 G4A frequency between cases and controls. CONCLUSIONS: This study implies an association of breast cancer risk with the p53 polymorphism Arg72Pro, but not with p73 G4A.     

Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population

p73, a structural and functional homologue of p53, shares some p53-like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell-cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case-control study of 425 lung cancer patients and 588 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26-0.80 and OR: 0.70, 95% CI: 0.53-0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele.     

PTTG和p53的表达与大肠癌淋巴结转移的关系

[目的]探讨垂体瘤转化基因(PTTG)和p53蛋白在大肠癌中的表达及其淋巴结转移的关系。[方法]采用免疫组织化学法检测71例大肠癌标本和42例癌旁正常黏膜组织的PTTG和p53蛋白的表达水平,并分析其与临床病理学特征的关系。[结果]PTTG蛋白和p53在大肠癌组织中的过度表达率分别为73.2%和70.4%,均明显高于其在正常大肠黏膜组织中的表达(7.1%和0),差异具有显著性(P<0.01)。PTTG的过度表达与淋巴结转移明显相关(P<0.001),p53的过度表达则与淋巴结转移不相关(P>0.05)。[结论]PTTG在大肠癌组织中呈过度表达,并与淋巴结转移有关,可以作为判断大肠癌是否有淋巴结转移的分子指标。     

Effects of p53 Codon 72 and MDM2 SNP309 Polymorphisms on Gastric Cancer Risk among the Iranian Population

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR(AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.     

Evidence that Expression of a Mutated p53 Gene Attenuates Apoptotic Cell Death in Human Gastric Intestinal-type Carcinomas in vivo

To examine in vivo the validity of the results of experiments in vitro , we analyzed the relationship between p53 gene status and apoptotic cell death of human gastric intestinal-type adenocarcinomas. Surgical specimens were classified into two categories: 18 gastric cancers with nuclear p53 protein (A), and 17 gastric cancers without nuclear p53 protein (B). Polyraerase chain reaction-single strand conformation polymorphism disclosed a shifted band that corresponded to a mutation in the p53 gene in 13 cases (72%) in category A and 3 cases (18%) in category B, the frequency being significantly higher in the former ( P <0.05). Apoptotic cells were identified from routinely stained sections and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The TUNEL index [TI: (the number of TUNEL-positive apoptotic cells/the total number of tumor cells) X100] was 3.8 ±1.4% in category A and 4.9 ±1.2% in category B, the value being significantly lower in the former ( P < 0.05). The proliferating cell nuclear antigen index, defined similarly to the TI, was 56.4±16.3% in category A, and it was significantly higher than that in category B ( P <0.05). The immunohistochemically detected expression of P21^CIP1/WAF1 did not differ between the two categories, while Bax-positive tumor cells were more frequently detected in category A. These results indicate that (1) expression of a mutated p53 gene attenuates apoptotic cell death of gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.     

Combined p53-related genetic variants together with HPV infection increase oral cancer risk

To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6]. After combining genotypes of seven polymorphisms and using the low-risk group (0-3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium-risk (4 combined risk genotypes) and high-risk groups (5-7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1-2.5) and 1.2 (95% CI, 0.7-1.9) for oral cancer risk, respectively, whereas the low-risk, medium-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2-3.6), 4.0 (95% CI, 1.8-9.1) and 19.1 (95% CI, 5.7-64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53-related genes may modify risk of HPV16-associated oral cancer, especially in young patients, never-smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.