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印度肺癌患者中18型人乳头瘤病毒感染与p53基因第72位密码子多态性

Infection of human papillomavirus type 18 and p53 codon 72 polymorphism in lung cancer patients from India.

作者信息

Jain Neeraj, Singh Vikram, Hedau Suresh, Kumar Suresh, Daga Mradul K, Dewan Richa, Murthy Nandagudi S, Husain Syed A, Das Bhudev C

机构信息

Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, I-7, Sector-39, Noida, 201301, India.

出版信息

Chest. 2005 Dec;128(6):3999-4007. doi: 10.1378/chest.128.6.3999.

DOI:10.1378/chest.128.6.3999
PMID:16354872
Abstract

STUDY OBJECTIVES

Infection with specific high-risk HPV types 16 and 18 and polymorphism of p53 codon 72 has been strongly associated with the genesis of various neoplasms in humans, but such study in lung cancer is limited and the results are controversial. In India, the role of these two factors has been strongly implicated in cervical and other cancers, but the occurrence of HPV or p53 codon 72 polymorphism has not been examined in lung cancer, which is the most common cause of cancer-related death in India.

DESIGN AND PATIENTS

A total of 40 tumor biopsy specimens from advanced lung cancer patients and blood samples from 40 matching control subjects were obtained for the analysis of high-risk HPV types 16 and 18 infection and p53 codon 72 polymorphism by polymerase chain reaction.

RESULTS

Only HPV type 18 was detected in 5% (2 of 40 lung cancer patients), but no other HPV could be detected. A significantly increased frequency of Arg/Arg homozygotes was observed in patients with advanced lung cancer when compared to that of control subjects (p = 0.004; odds ratio, 5.13; 95% confidence interval, 1.59 to 17.26). However, no significant correlation could be made between p53 polymorphism and different clinical stages, except for advanced stage IV patients, who showed a higher proportion of Arg/Pro heterozygous genotype.

CONCLUSIONS

HPV detected in a small proportion of lung cancer patients in India demonstrated an exclusive prevalence of HPV type 18, and there was a significantly higher frequency of p53 Arg/Arg genotype when compared to that of control subjects. Observation of a shorter duration of symptoms (< or = 4 months) in as many as 78% (seven of nine stage IV patients) with Arg/Pro genotype may be an indication that lung cancer patients with the heterozygous p53 genotype are more susceptible to early progression.

摘要

研究目的

特定高危人乳头瘤病毒16型和18型感染以及p53基因第72密码子多态性与人类多种肿瘤的发生密切相关,但肺癌方面的此类研究有限且结果存在争议。在印度,这两个因素在宫颈癌和其他癌症中作用显著,但在肺癌中HPV感染情况或p53基因第72密码子多态性尚未得到研究,而肺癌是印度癌症相关死亡的最常见原因。

设计与患者

共获取40例晚期肺癌患者的肿瘤活检标本以及40例匹配对照者的血液样本,通过聚合酶链反应分析高危人乳头瘤病毒16型和18型感染及p53基因第72密码子多态性。

结果

仅在5%(40例肺癌患者中的2例)检测到HPV 18型,未检测到其他HPV类型。与对照者相比,晚期肺癌患者中Arg/Arg纯合子频率显著增加(p = 0.004;优势比,5.13;95%置信区间,1.59至17.26)。然而,除了晚期IV期患者显示出较高比例的Arg/Pro杂合基因型外,p53多态性与不同临床分期之间无显著相关性。

结论

在印度一小部分肺癌患者中检测到的HPV显示仅HPV 18型流行,与对照者相比,p53 Arg/Arg基因型频率显著更高。在多达78%(9例IV期患者中的7例)具有Arg/Pro基因型的患者中观察到症状持续时间较短(≤4个月),这可能表明p53杂合基因型的肺癌患者更易早期进展。

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