Investigating the Role of HPV in Lung Cancer

研究 HPV 在肺癌中的作用

• 批准号: 8384968
• 负责人: Camille C. Ragin
• 金额: $ 7.99万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8384968
• 关键词: Investigating; Role; HPV; Lung; Cancer

ABSTRACT: Cigarette smoking is the primary risk factor for lung cancer and there are gender differences in the relationship between smoking and this disease. The contributions of genetic risk factors and tobacco exposure to lung cancer development have been studied. Furthermore combined effect of genetic polymorphisms in CYP1A1 and GSTM1 (phase I and II enzymes that metabolize tobacco carcinogens) is reported to be associated with a higher risk of lung cancer among women than men (OR = 6.54 vs. 2.36). Lung cancer can develop among about 10% of subjects with no prior history of cigarette smoking. Therefore, risk factors other than cigarette smoking may attribute to the development of some lung tumors. Human Papillomavirus (HPV) causes cervical cancer in women and is associated with most other anogenital cancers as well as oropharngeal cancers in both men and women. Some studies have suggested that HPV may be associated with a subset of lung tumors, although an etiologic link has not been firmly established. We and others have suggested that HPV may play a role in the development of second primary lung cancers in women who had a first diagnosis of cervical cancer. It is not yet clear, whether HPV may contribute to the gender differences in lung cancer development. However further investigation of the role of HPV in lung cancer among women is warranted. Gene-viral interactions in lung cancer have not been studied. However, one In vitro study reports that GSTM1 expression is lower in cells that express the HPV oncoproteins. If HPV is associated with lung cancer development, it is possible that this virus will play an additional role in the subject's ability to handle tobacco carcinogenesis since expression of the GSTM1 protein helps to prevent the damaging effects of tobacco carcinogens through their detoxification. We hypothesize that gender differences in lung cancer may be associated with HPV infection. We propose to first perform a pooled analysis of cross-sectional studies to study the association of HPV in lung tumors and second, perform a cross-sectional study to investigate the relationships of HPV, GSTM1 and CYP1A1 polymorphisms in male and female lung cancer patients. There are no studies that have investigated gene-viral-environment relationships in lung cancer. The goal of this study is to evaluate the prevalence of HPV among lung cancer cases and to explore the possible gene-viral interactions in this disease. Our long term goal is to better understanding of gender-specific differences in lung cancer development. We expect that these proposed studies will help to shape our investigation of gender differences in lung cancer.

摘要：吸烟是肺癌的首要危险因素，吸烟与肺癌的关系存在性别差异。遗传风险因素和烟草暴露对肺癌发展的影响已经得到研究。此外，据报道，CYP1A1 和 GSTM1（代谢烟草致癌物的 I 相和 II 相酶）基因多态性的综合效应与女性患肺癌的风险高于男性相关（OR = 6.54 vs. 2.36）。约 10% 以前没有吸烟史的受试者可能会患上肺癌。因此，吸烟以外的危险因素也可能导致某些肺部肿瘤的发生。人乳头瘤病毒 (HPV) 会导致女性宫颈癌，并与大多数其他肛门生殖器癌症以及男性和女性口咽癌相关。一些研究表明，HPV 可能与一部分肺部肿瘤有关，尽管其病因学联系尚未确定。我们和其他人提出，HPV 可能在首次诊断出宫颈癌的女性第二原发性肺癌的发展中发挥作用。目前尚不清楚 HPV 是否可能导致肺癌发展的性别差异。然而，有必要进一步研究 HPV 在女性肺癌中的作用。肺癌中的基因-病毒相互作用尚未研究。然而，一项体外研究报告称，表达 HPV 癌蛋白的细胞中 GSTM1 表达较低。如果 HPV 与肺癌的发展有关，那么这种病毒可能会在受试者处理烟草致癌的能力中发挥额外的作用，因为 GSTM1 蛋白的表达有助于通过解毒来防止烟草致癌物的破坏性影响。我们推测肺癌的性别差异可能与 HPV 感染有关。我们建议首先进行横断面研究的汇总分析，以研究 HPV 与肺癌之间的关联，其次，进行横断面研究以调查男性和女性肺癌患者中 HPV、GSTM1 和 CYP1A1 多态性的关系。目前尚无研究调查肺癌中基因-病毒-环境关系的研究。本研究的目的是评估肺癌病例中 HPV 的患病率，并探讨该疾病中可能的基因-病毒相互作用。我们的长期目标是更好地了解肺癌发展中的性别差异。我们期望这些拟议的研究将有助于我们对肺癌性别差异的调查。