p53 Arg72Pro多态性与新疆维吾尔族宫颈癌的相关性

目的 探讨p53 Arg72Pro多态性与新疆维吾尔族宫颈癌发生的相关性。方法 采用PCR-RFLP和PCR方法检测152例维吾尔族宫颈癌组织和110例维吾尔族正常宫颈组织中p53Arg/Arg、Pro/Pro、Arg/Pro3种基因型的分布和HPV16DNA。结果 p53基因型Arg/Arg、Pro/Pro、Arg/Pro在维吾尔族宫颈癌中的分布频率为46.0%、13.2%、40.8%,对照组为30.0%、14.5%、55.5%,两组总构成比差异有统计学意义（χ^2=7.196,P〈0.05）,Arg/Arg在宫颈癌中所占比例高于其它两个基因型,且高于对照组中Arg/Arg的比例。维族宫颈癌患者HPV16阳性率为74.3%。在维族宫颈癌组中,HPV16阳性组p53基因型Arg/Arg、Pro/Pro、Arg/Pro的分布频率为48.7%、8.8%、42.5%,HPV16阴性组为38.5%、25.6%、35.9%,两组总构成比差异有统计学意义（χ^=7.177,P〈0.05）。结论 p53 Arg72Pro多态性可能与新疆维吾尔族宫颈癌发生相关,p53 Arg/Arg基因型可能是新疆维吾尔族宫颈癌发生的遗传易感因素,且与维吾尔族HPV相关宫颈癌的发生有关。     

p53基因第72位密码子多态性与宫颈癌相关性

目的　探讨 p5 3基因第 72位密码子多态性与新疆汉族人群宫颈癌发生的关系。 方法　采用限制性酶切片段多态性分析 (RFLP)技术检测 72例宫颈癌及正常宫颈石蜡包埋组织中p5 3基因多态性的分布 ,分析两者之间的相关性。结果　p5 3基因 3种基因型Arg/Arg、Pro/Pro、Pro/Arg在宫颈癌中所占比例分别是 2 1 0 % ,39 5 % ,39 5 % ,对照组为 38 2 % ,14 7% ,4 7 1% ,两组总构成比差异有显著性 (χ2 =6 0 1,P <0 0 5 ) ,Pro/Pro在宫颈癌中所占比例高于对照组 ,没有发现Arg/Arg在宫颈癌中所占比例高于对照组 ,在HPV16、18阳性宫颈癌中所占比例分别是 2 2 2 % (4 /18)、5 0 0 % (9/18)、2 7 8% (5 /18) ,Pro/Pro所占比例明显高于其它两型。结论　p5 3Pro/Pro基因型可能是新疆汉族女性宫颈癌主要遗传易感因素。     

喀什维吾尔族宫颈癌患者HPV16型感染及其人类白细胞抗原-DQB1基因多态性的关系

目的 探讨HPV16型病毒感染与宿主人类白细胞抗原HLA-DQB1基因多态性和喀什维吾尔族宫颈癌发生的相关性.方法 采用导流杂交基因芯片技术及聚合酶联反应序列特异性寡核苷酸探针(Polymerase chain reaction sequence-specific oligonucleotide ,PCR-SSO)法检测111例喀什维吾尔族宫颈癌患者、100例正常妇女宫颈组织HPV感染及型别分布和HLA-DQB1的等位基因.结果 (1)111例宫颈癌患者中,HPV总感染率81.9%(91/111),其中HPV16型感染占的比例最高,为91.2%(83/91),100例正常宫颈组织中HPV阳性者为9例,阳性率为9.00%(9/100),其中HPV16阳性2例,两组之间差异有显著性(P<0.01).(2)HLA-DQB1·03在宫颈癌组中出现的频率明显低于对照组,两组之间差异有统计学意义(χ2=4,P=0,OR=0.607,95% CI=1.042～2.478).HLA-DQB1·06在宫颈癌组中出现的频率明显高于对照组,两组之间差异有统计学意义(χ2=7.112、P=0,OR=2,95% CI=1.204～3.549).宫颈癌中HLA-DQB1·06阳性者HPV16的感染率明显高于阴性者(χ2=4.907,P=0.027,OR=2,95% CI=1.092～6.840),两组比较差异有统计学意义,说明携带HLA-DQB1·06等位基因的维吾尔族妇女更容易被HPV16感染.HLA-DQB1的其他等位基因在宫颈癌组及对照组中出现的频率差异无显著性(P>0.05).结论 HLA-DQB1·03可能为维吾尔族妇女宫颈癌的保护基因,而HLA-DQB1·06可能与维吾尔族妇女对宫颈癌的遗传易感性有关,是维吾尔族妇女对宫颈癌的易感基因,HLA-DQB1·06基因型可能增加了HPV16 阳性妇女患宫颈癌的危险性,可能是维吾尔族妇女宫颈癌患病率高的原因之一.维吾尔族妇女宫颈癌易感基因及保护基因的检测可能在高危人群的检测及群体遗传干预工作中有一定的指导意义.     

瘢痕疙瘩p53基因检测试剂盒的临床实验

目的:对瘢痕疙瘩p53基因检测试剂盒进行临床实验,评价此试剂盒的准确度和有效性。方法:运用聚合酶链反应-反向斑点杂交、DNA直接测序方法,检测52例临床瘢痕疙瘩患者和配对的52例正常人p53基因第72位密码子的基因型。结果:瘢痕疙瘩患者的Pro等位基因频率和Pro/Pro基因型频率明显高于对照组(χ2=6.268,P=0.018;χ2=11.34,P=0.01),而Pro/Arg型和Arg/Arg型未见有统计学差异。结论:p53基因第72位密码子Pro等位基因及Pro/Pro基因型是中国广东地区人群对瘢痕疙瘩的易感因素,瘢痕疙瘩p53基因检测试剂盒具有良好的可重复性和特异性。     

新疆维、汉两民族健康人群KCNEl基因多态性分布

目的研究心肌钾离子通道B亚单位基因（potassiumvoltage．gatedchannel,Isk—relatedfamily,member1,KCNEl）标签SNPrs2834497和rs4817656在新疆维吾尔族和汉族健康人群中的分布情况。方法选择新疆地区409名维吾尔族和406名汉族,均为健康人群,采用等位基因特异性PCR（allele—specificpolymerasechainreaction,AS—PCR）方法进行基因分型。结果①rs2834497三种基因型AA型、AG型和GG型在维吾尔族人群中的分布频率分别为：65．5％、29．8％和4．6％;在汉族人群中的分布频率分别为：55．4％、36．9％和7．6％,两组基因型分布比较有统计学意义（χ^2=9．92,P〈0．01）;②rs4817656三种基因型cc型、cT型和TT型在维吾尔族人群中的分布频率分别为：26．4％、53．5％和20．0％;在汉族人群中的分布频率分别为：22．2％、49．0％和28．8％。两组基因型分布比较有统计学意义（χ^2=8．74,P〈0．05）;③rs4817656和rs2834497共构建4个单体型,其中CG和删单体型在维族中的分布明显高于汉族（χ^2=37．83,P〈0．01;,=4．13,P〈0．05）,％单体型在汉族中的分布明显高于维族（χ^2=30．77,P〈0．01）。结论KCNEl基因标签SNPrs2834497和rs4817656在新疆汉族和维吾尔族健康人群中的分布差异具有统计学意义。     

p53基因第72位密码子多态与食管癌风险

目的 研究p53基因第７２位密码子Ａrg/Pro多态与食管癌遗传易感性的关系。方法 采用聚合酶链反应－－限制性片段长度多态性方法检测了９１例食管癌患者与２０４名正常对照组的p53 Arg/Pro基因型分布及差异。结果 正常对照组p53 Pro等位基因频率（０.588）与病例组（０.480）比较差异无显著性（Ｐ＝０.11）。但３种p53基因型频率在病例组和对照组的分布差异有显著性，病例组的Ｐro/Pro基因型频率（３９.6％）显著高于对照组（２１.1%）。携带Ｐro/Pro纯合变异基因型者患食管癌的风险比携带Ａrg/Arg纯合野生基因型者高２倍[校正比值比（odds ratio,OR）为２.18,95%可信区间（confidemce interval,CI）为１.10-4.35。杂合子基因型（Ａrg/Pro）与食管癌的遗传易感性无关（校正ＯＲ＝０.84％，９５％ＣＩ＝０.42－１.68）。吸烟增加食管癌风险（ＯＲ＝２.30,95%CI=1.30-4.12)，但与Ｐro/Pro基因型无协同作用。结论 p53基因第７２位密码子纯合突变是中国人的食管癌易感因素。     

中国汉族和维吾尔族RHD基因结构的比较研究

目的对比研究中国汉族和新疆维吾尔族随机非血缘关系RhD阴性个体RHD基因结构。方法采用序列特异性引物．聚合酶链反应方法检测RHD基因的上、下游和杂交的Rhesus盒，以及RHD基因的10个外显子。结果RhD阴性个体RHD基因型检测结果显示，新疆维吾尔族人与同组汉族人RHD^-／RHD^-基因型组差异有统计学意义（94．44％vs61．40％，P〈0．01），两者与RHD^＋／RHD^-基因型组（该组代表RHD单基因组）比较差异有统计学意义（2．78％vs34．21％，p〈0．01），但与RHD^＋／RHD^＋型组比较差异无统计学意义（2．78％vs4．39％，P〉0．05）。78名汉族RhD阴性个体RHD单基因结构研究显示，53名（67．95％）为RHD（1-10）型（其中非表达的14名），15名（19．23％）为RHD-CE（2．9）．晚基因型，5人（6．4l％）为RHD-CE（2-7）-D2基因型，2人（2．56％）与RHD-CE（3-6）-D型相似，1人（1．28％）为RHD．CE（5．6）．D型，2人为RHD-CE（6）-D或点突变。2名新疆维吾尔族RhD阴性个体RHD单基因型中1人为RHD（1-10）型，1人为RHD-CE（2-9）-02。结论汉族RhD^-／RHD^＋单基因型最常见非表达的等位基因依次为RHD-CE（2-9）-D2、RHD（1-10）、RHD-CE（2-7）-D2。新疆维吾尔族携带汉族常见而在白人罕见的非表达的RHD等位基因RHD-CE（2-9）-D2，显示维吾尔族和汉族两大民族基因的融合特征。     

新疆妇女子宫颈病变组织中HPV16E6基因突变分析

目的通过检测HPV16E6基因突变在新疆维吾尔族和汉族妇女宫颈癌组织中的分布规律,以探讨该突变与宫颈癌发生的关系。方法取汉族宫颈炎(含石蜡包埋组织及宫颈刷液基标本)125例,维吾尔族宫颈炎(含石蜡包埋组织及宫颈刷液基标本)124例;汉族石蜡包埋宫颈癌35例,维吾尔族石蜡包埋宫颈癌共109例。用以上HPV16阳性DNA模板PCR扩增HPV16E6全长基因,PCR产物直接测序,分析新疆女宫颈癌组织HPV16E6基因的突变。结果PCR检测结果显示汉族族宫颈炎组织中HPV16E6阳性率为35.71%(15/42);维吾尔族宫颈炎组织中HPV16E6阳性率为30.46%(14/46);汉族族宫颈癌组织中HPV16E6阳性率为33.33%(2/6),维吾尔族宫颈癌组织中HPV16E6阳性率为22.22%(12/54);宫颈炎与宫颈癌中HPV16E6阳性表达无统计学意义(P>0.05),对21份(上皮内低度病变1例,原位癌1例,低分化宫颈癌4例,中分化宫颈癌4例,高分化1例,轻度炎症4例,中度炎症3例,重度炎症1例,正常宫颈2例)HPV16E6扩增片段的双向测序,其中5例成功测序得到一级结构,并且序列分析表明,2例(维吾尔...     

新疆南部地区维吾尔族妇女宫颈癌组织中HPV-16型L2基因多态性分析

目的探讨新疆南部地区维吾尔族妇女宫颈癌组织中人乳头瘤病毒16型(humanpapillomavirus16,HPV16)L2基因的变异,并预测L2蛋白的功能变化。方法从19份中国新疆南部地区维吾尔族妇女宫颈癌活检组织标本中提取DNA,以此DNA为模板,PCR扩增HPV16L2全长基因,PCR产物直接测序或克隆后测序,分析新疆维吾尔族妇女宫颈癌组织HPV16L2基因多态性及HPV16L2蛋白功能的变化。结果PCR检测结果显示宫颈癌组织中HPV16L2阳性率为84.21%(1619);测序和序列分析表明L2基因核苷酸多处发生变异,并引起编码氨基酸的变异;L2基因在核苷酸水平上形成7种突变模式(XJL21～XJL27),各模式与HPV16原型比较,同源性在99.37%～99.79%之间;在氨基酸水平上形成5种突变模式,其中XJL1123突变模式占66.67%(812),是突变的主流模式,各模式与HPV16原型比较,同源性在98.31%～99.58%之间;以上突变引起HPV16L2蛋白疏水性和抗原性的改变,继而改变了L1蛋白的结构及功能。结论中国新疆南部地区维吾尔族妇女宫颈癌组织中HPV16L2基因发生多位点变异,并形成多种突变模式和突变主流模式;这些突变引起HPV16L2蛋白疏水性和抗原性的改变,提示HPV16L2基因突变可能与HPV16的系统发生以及病毒逃避机体免疫识别有关。     

新疆地区贲门腺癌HPV、HP感染和p53异常改变的病理生物学意义

目的了解人乳头瘤病毒（HPV）、幽门螺杆菌（HP）感染及p53突变在新疆不同民族贲门癌发生、发展中的作用。方法应用PCR技术对90例贲门腺癌（包括哈族29例,维族30例,汉族31例;癌组织高、中、低不同分化程度分别有17、55、18例）及21例切缘正常组织进行HPV16／18和HP的检测,并用免疫组化LSAB法检测以上病例的p53异常表达;同时应用上述不同方法分别检测20例胃窦部腺癌HPV16／18、HP感染和p53的表达。结果HPV16／18和HP感染及t）53在新疆贲门腺癌患者中的阳性检出率分别为34．4％（31／90）,14．4％（13／90）和73．33％（66／90）,在切缘正常组织中的检出率分别为0、0、4．76％（1／21）;它们的阳性检出率在癌和非癌组织间差异均存在显著性（P〈0．05）;哈、维、汉各民族之间HPV16／18、HP及p53的阳性率的差异均无统计学意义（P〉0．05）;HPV16／18和HP感染阳性率与贲门腺癌病理分级及淋巴结转移无明显相关（P〉0．05）;p53的阳性表达与组织分级无关（P〉0．05）,而与淋巴结转移相关（P〈0．05）;贲门腺癌患者中p53与HPV16／18和HP的感染之间未发现相关关系（P〉0．05）。胃窦部腺癌患者中HPV16／18及HP阳性检出率分别为10％（2／20）、55％（11／20）与其在贲门腺癌的阳性检出率差异有显著性（P〈0．05）,胃窦部腺癌组织中p53的阳性检出率为80％（16／20）,与其在贲门腺癌的阳性检出率差异无显著性（P〉0．05）。结论（1）HPV16／18感染和p53的异常表达在贲门癌变过程中可能具有重要的作用,而HP感染与贲门癌的发生关系不大;胃窦部HPV16／18感染率较低,而HP感染检出率较高;（2）贲门癌组织中HPV16／18、HP感染和p53的异常表达与肿瘤病理分级和民族之间均无明显相关;p53的阳性表达与淋巴结转移相关;（3）p53的异常表达与HPV16／18或HP感染在胃贲门、幽门区腺癌的发生可能均有重要作用。     

p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women

A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.     

Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for patients with squamous epithelial lesion of the uterine cervix

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene in association with human papillomavirus (HPV) 16 E6 variants has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. The association of p53 codon 72 polymorphism alone and in combination with specific HPV 16 E6 variants with risk of developing squamous intraepithelial cervical lesion has been investigated in low and high‐grade squamous intraepithelial lesions and in HPV‐negative controls from an Italian population. The data obtained showed statistically significant different distribution of p53 genotypes between healthy controls and precursor lesions, with the p53 arginine homozygous increased in high‐grade squamous intraepithelial lesions. The T350G HPV 16 variant was the most frequent variant observed in the analyzed group of Italian women, showing a slight decreasing with the severity of the lesion. At the same time, the number of the prototype T350 slightly increased with the severity of the cytological lesions. In conclusion, p53 arginine homozygous was found to be increased in high‐grade lesions, supporting the results of previous investigations indicating that HPV‐positive patients with p53 Arg/Arg have an increased risk of developing pre‐cancerous lesions. In addition, T350G HPV 16 variant was over‐represented in p53 Arg homozygous women with cervical lesions. When p53 genotype and HPV 16 variants are considered together, no difference emerges between cases and controls so is not possible to assess that the oncogenic effect of HPV 16 T350G variant may be influenced by the p53 genotype. J. Med. Virol. 85:83–90, 2012. © 2012 Wiley Periodicals, Inc.     

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.     

P53 codon 72Arg polymorphism is not a risk factor for carcinogenesis in the chinese.

The potential association of distinct polymorphism of the tumor suppressor gene p53, with an increased susceptibility to malignant transformation has been reported for various cancers. A polymorphism at codon 72 of p53 results in translation to either arginine (p53Arg) or proline (p53Pro), and recent study showed that Caucasian women with arginine form of p53 are more susceptible to HPV-associated carcinoma of the cervix. To examine whether arginine 72 could be a significant risk factor for tumor development, we used a PCR-based assay to analyze p53 genotypes of patients for several types of carcinoma. No significant difference in the frequency of p53Arg was found between normal and cancer patients, the results showed that the individuals homozygous for arginine variant were not at increased risk for cancer.     

The p53 R72P polymorphism does not influence cervical cancer development in a Portuguese population: a study in exfoliated cervical cells

The interaction between the E6 protein of the high-risk human papillomaviruses (HPVs) with p53 seems to be crucial in cervical carcinogenesis. The presence of Arg/Arg genotype at codon 72 of TP53 gene was characterized as a risk factor in development of cervical cancer. However, the role of this polymorphism remains controversial and some authors suggested that the origin of DNA (blood or exfoliated cervical cells) might influence these results. This study analyzed the effect of the p53 codon 72 polymorphism (R72P) in exfoliated cervical cells of women from the northern region of Portugal using two methodologies: allele-specific polymerase chain reaction and real-time polymerase chain reaction. We studied 700 cervical exfoliated cells which showed: 334 cases from women without cervical cancer or cervical lesion (N), 114 low-grade squamous intraepithelial lesions (LSIL), 107 high-grade squamous intraepithelial lesions (HSIL), 20 invasive cervical cancers (ICC) and 125 atypical squamous cells of unknown significance (ASCUS). No statistically significant differences between cases and controls were found, regarding the influence of the R72P polymorphism with cytological classification, high risk-HPV infection and HPV16 presence (P = 0.336, P = 0.945, and P = 0.964, respectively). Also, the influence of this polymorphism in the median age of onset for LSIL, HSIL, and ICC was not statistically significant (P = 0.674, P = 0.810, and P = 0.928, respectively). Therefore, the hypothesis that women with Arg/Arg genotype have an increased risk of developing cervical cancer failed to be proven in this study. Moreover, our study reveals that results using exfoliated cervical cells are reliable as compared with studies on blood.     

Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations

Human papillomavirus (HPV) is the necessary cause for cervical cancer development, and the interaction of HPV-E6 with p53 is known as the most important event in HPV-associated carcinogenesis. In vitro studies have suggested that HPV-E6 interacts more efficiently with the arginine (Arg) p53 variant at position 72 as it appears to be more susceptible to degradation through the ubiquitin proteasome pathway. However, few reports have corroborated this data, and the role of the p53 codon 72 polymorphism in the development of cervical cancer requires further elucidation. We performed a meta-analysis review of all studies published within European populations to summarize the overall risk of this polymorphism considering the influence of the geographical/ethnic location as an important factor in defining a genetic profile and the susceptibility for cervical cancer development. Our analysis revealed that the p53 Arg/Arg genotype does not seem to represent a risk marker for the development of cervical lesions in the majority of the European countries analysed. However, in countries with low incidence rates of cervical cancer, this polymorphism might represent a significant genetic marker.     

p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1

Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination of inhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an important role is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and the interaction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthy subjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphism and allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is present in subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype is significantly high in asthmatic children than in controls (OR=1.941; 95% C.I. 1.042-3.628). Our finding could have important clinical implications since the subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype.     

Interplay between human papilloma virus infection and p53 gene alterations in head and neck squamous cell carcinoma of an Indian patient population

AIM: To investigate the complex interplay between human papilloma virus (HPV) infection and p53 gene alteration in 92 head and neck squamous cell carcinoma (HNSCC) and 28 leukoplakia samples from eastern India. METHODS: DNA isolated from the patient samples was subjected to HPV detection, loss of heterozygosity (LOH) analysis of the chromosome 17p region harbouring p53, genotyping at the p53 codon 72 locus and sequencing of the entire p53 gene to identify somatic mutations. Codon 72 heterozygotes carrying the p53 mutation were further cloned and resequenced to identify the allele harbouring the mutation. RESULTS: HPV positivity in the HNSCC samples was 69%; 21% of the HNSCC were found to harbour p53 mutations in the coding region of the gene. The absence of the p53 mutation in HPV positive tumours was statistically significant compared to the HPV negative tumours (p = 0.01), but the same did not hold true for p53 LOH (p = 1.0). Among the germline p53 codon 72 heterozygotes, the Pro allele was preferentially lost (p = 0.02) while the Arg allele was mutated in the majority of cases. The risk of HPV mediated tumourigenesis increased with the increase in number of Arg alleles at the codon 72 locus. CONCLUSION: It is proposed that genetic and epigenetic alteration of p53 follow distinct pathways during the development of HNSCC from normal epithelium via dysplasia. The p53 mutation and HPV mediated p53 inactivation possibly constitute two independent pathways of tumourigenesis.     

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.     

Predisposition to HPV16/18-related cervical cancer because of proline homozygosity at codon 72 of p53 among Indian women is influenced by HLA-B*07 and homozygosity of HLA-DQB1*03

This study was undertaken to examine whether predisposition to human papillomavirus (HPV)16/18-related cervical cancer (CaCx) because of p53 proline homozygosity (Pro72Pro) among Indian women was mediated singly or jointly with immunogenetic risk factors such as HLA-B*07 or homozygosity of HLA-DQB1*03. Molecular detection of all three genetic factors was performed by polymerase chain reaction-restriction fragment length polymorphism using DNA from (i) 114 CaCx samples (78 HPV16/18 positive) and (ii) 195 cytologically normal cervical scrapes (116 HPV-negative and 79 HPV16/18-positive samples). Multiple logistic regression analyses were performed to examine independent effects of the three factors and to determine age-adjusted odds ratio (OR) [95% confidence interval (CI)] and P-values. HLA-B*07 was observed to be significantly associated with HPV16/18 infection in asymptomatic controls (OR(age-adjusted) = 4.73; 95% CI: 1.55-14.45; P = 0.006) and CaCx (OR(age-adjusted) = 6.14; 95% CI: 2.15-17.53; P < 0.001) in this enhanced sample set of CaCx cases. There was a lack of association between HLA-B*07 and HLA-DQB1*03 in our study samples. The association of p53Pro72Pro with CaCx was non-significant in the absence of HLA-B*07 in HPV16/18-positive women. In this group, prevalence of p53Pro72Pro and HLA-B*07 together was significantly higher (7.0%) among CaCx cases (OR(age-adjusted) = 14.05; 95% CI: 1.11-177.30; P = 0.04), compared with controls (1.3%) lacking both factors. HLA-DQB1*03 homozygosity (OR(age-adjusted) = 4.75; 95% CI: 1.17-19.30; P = 0.03) or p53Pro72Pro (OR(age-adjusted) = 5.84; 95% CI: 1.18-28.99; P = 0.03) was found to be significantly associated with CaCx, each in the absence of the other in this group but not when present jointly in contrast to those lacking both factors (P = 0.214). Thus, modulation of p53Pro72Pro-mediated susceptibility to CaCx by immunogenetic factors could possibly be mediated through cross talk between HPV16/18-induced immune evasion and cell transformation.