Investigating the Role of HPV in Lung Cancer

描述(申请人提供)：摘要：吸烟是肺癌的主要危险因素，吸烟与肺癌的关系存在性别差异。已经研究了遗传风险因素和烟草暴露对肺癌发生的贡献。此外，据报道，CYP1A1和GSTM1(代谢烟草致癌物的I和II相酶)基因多态的共同作用与女性患肺癌的风险比男性更高(OR=6.54比2.36)。约10%的无吸烟史的受试者会患上肺癌。因此，吸烟以外的其他危险因素可能与一些肺癌的发生有关。人乳头瘤病毒(HPV)导致女性宫颈癌，并与大多数其他肛门生殖道癌以及男性和女性的口咽癌有关。一些研究表明，HPV可能与肺肿瘤的一个子集有关，尽管病因联系尚未确定。我们和其他人提出，在首次诊断为宫颈癌的女性中，HPV可能在第二原发癌的发生中发挥作用。目前尚不清楚HPV是否会导致肺癌发生的性别差异。然而，有必要进一步研究HPV在女性肺癌中的作用。基因-病毒在肺癌中的相互作用还没有研究。然而，一项体外研究报告称，在表达HPV癌蛋白的细胞中，GSTM1的表达较低。如果HPV与肺癌的发展有关，这种病毒可能会在受试者处理烟草致癌的能力方面发挥额外的作用，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。我们假设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合并分析，以研究HPV与肺部肿瘤的相关性，然后进行横断面研究，以调查男性和女性肺癌患者中HPV、GSTM1和CYP1A1基因多态的关系。目前还没有研究肺癌基因-病毒-环境关系的研究。本研究的目的是评估HPV在肺癌患者中的流行情况，并探索在这种疾病中可能的基因-病毒相互作用。我们的长期目标是更好地了解肺癌发生过程中的性别差异。我们期望这些拟议的研究将有助于形成我们对肺癌性别差异的研究。

DESCRIPTION (provided by applicant): 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.