MOLECULAR CYTOGENETIC STUDY OF LUNG CANCER

本研究基于一项正在进行的少数民族肺癌病例对照研究的流行病学、分子和细胞遗传学数据。诱变原敏感性，基于定量的博来霉素诱导的染色单体断裂，与肺癌风险显著增加相关。我们还报道了这些断裂似乎优先发生在5号染色体上。我们现在计划将这些细胞遗传学发现在外周血淋巴细胞中扩展到目标（肺）组织，使用中期制剂、培养的肿瘤细胞、石蜡切片和已经处理和储存的冷冻肿瘤组织。具体目标是：

This study is based upon the epidemiologic, molecular and cytogenetic data from an ongoing case-control study of lung cancer in minority populations. Mutagen sensitivity, based on quantifying bleomycin-induced chromatid breaks, was associated with significantly increased lung cancer risk. We have also reported that these breaks seem to occur preferentially on chromosome 5. We now plan to extend these cytogenetic findings in peripheral lymphocytes to target (lung) tissue using metaphase preparations, cultured tumor cells, paraffin sections, and frozen tumor tissue which have already been processed and stored. The specific aims are: 1) To compare paired specimens of lung tumor and adjacent normal tissue with lymphocytes from 60 lung cancer patients to assess concordance of abnormalities on chromosome 5 using chromosome painting probes as well as with PCR-based microsatellite repeat polymorphism (MSRP) assay on Sq. The working hypothesis is that the predilection of Sq to mutagenic damage may be a marker of susceptibility to lung cancer. 2) To confirm our preliminary findings that the survival rate of cells with Sq aberrations in cases is significantly higher than that in controls, using whole chromosome 5 painting probe in 100 lung cancer cases and 100 frequency matched controls. The hypothesis being tested is that only those breakpoints that contain the loci of important genes and continue to survive and proliferate in the target tissue could contribute to neoplastic transformation. 3) To assess the associations between our findings from specific aims 1 and 2 with cigarette smoking, occupational exposure, family history and lung cancer risk by integrating epidemiologic data with the cytogenetic, molecular cytogenetic and molecular genetic (including metabolic polymorphism) data. We will test the hypothesis that cancer risk is increased in individuals who have one or more susceptible genetic trait and the relevant carcinogenic exposures. The long term goal is to further the understanding of the mechanism of mutagen sensitivity and its implication for lung carcinogenesis.