A genomewide study of lung cancer in never smokers

对从不吸烟者进行肺癌的全基因组研究

• 批准号: 8444716
• 负责人: Olga Gorlova
• 金额: $ 36.46万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8444716
• 关键词: Age; Architecture; Asbestos; Bioinformatics; Biology; Blood specimen; Canada; Cancer Etiology; Candidate Disease Gene; Caucasians; Caucasoid Race; Cessation of life; Cigarette; Classification; Clinic; Clinical Data; Colon Carcinoma; Country; Data; Development; Disease; Environmental Risk Factor; Environmental Tobacco Smoke; Epidemiology; Europe; Gender; Genes; Genetic; Genome; Genotype; Institutes; International; Israel; Joints; Light; Logistic Regressions; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Molecular; NCI Center for Cancer Research; North America; Pathway interactions; Patient Self-Report; Patients; Phase; Population; Predisposition; Prevention; Public Health Schools; Recording of previous events; Research Institute; Resources; Risk; Risk Factors; Sample Size; Sampling; Site; Smoke; Smoker; Smoking; Smoking Behavior; Staging; Testing; The Sun; Tobacco smoke; Tobacco smoking; Trees; Universities; University of Texas M D Anderson Cancer Center; anticancer research; base; cancer risk; case control; drug mechanism; experience; gene environment interaction; genetic epidemiology; genome wide association study; genome-wide; killings; malignant breast neoplasm; never smoker; non-smoker; public health relevance; response; tool

DESCRIPTION (provided by applicant): Lung cancer remains the leading cause of cancer death, killing more patients than breast, colon, and prostate cancers combined. Although tobacco smoke is the predominant risk factor for development of lung cancer, some patients develop the disease without a history of tobacco smoking. About 10 - 15% of all lung cancers occur in lilfetime never smokers. This figure will increase as the proportion of never smokers increases in the population. Even at present rates, lung cancer in never smokers, if considered a separate disease, is 7th to 9th top cause of cancer death. The growing number of never smokers in the USA and other countries emphasizes the importance of understanding the epidemiology and biology underlying lung cancer in this group. Epidemiological, molecular and clinical data suggest that molecular mechanisms of lung cancer may differ in smokers and nonsmokers, making lung cancer in never smokers a different disease compared to the lung cancer in smokers. The genetic epidemiology of lung cancer in never smokers has not been well explored, largely because of difficulties in accruing the needed sample size for association studies. We propose a multicenter (total 22 sites from North America, Israel, and Europe) genomewide association study of lung cancer in never smokers with the following specific aims: Aim 1: Discovery phase: To identify candidate SNPs influencing the risk for lung cancer in never smokers. This phase will include 1553 never smoker lung cancer cases and 1553 controls matched on age, gender, and study site. Aim 2: Replication phase: To perform replication analysis of significant SNPs identified in the Discovery phase, using an independent set of cases and controls from International Lung Cancer Consortium (ILCCO) studies. There will be 1581 independent cases and 1581 matched controls in this phase. Aim 3: To identify and explore pathways associated with the risk of lung cancer in never smokers. To explore the effects of gene-gene and gene-environment interactions on lung cancer risk in never smokers. This will be the first GWAS aiming at identifying the genetic control of susceptibility to lung cancer in Caucasian never smokers. We will combine the available resources from the multiple sites to achieve the sample size sufficient for this study. The study will identify genetic architecture of the predisposition to the lung cancer in never smokers.

描述（由申请人提供）：肺癌仍然是癌症死亡的主要原因，杀死患者比乳腺癌，结肠癌和前列腺癌的总和更多。尽管烟草烟雾是肺癌发展的主要危险因素，但一些患者患有疾病而没有烟草吸烟史。所有肺癌中约有10-15％发生在Lilfetime从不吸烟者中。随着人口中的永不吸烟者的比例增加，这个数字将会增加。即使以目前的速度，如果被认为是单独的疾病，则无吸烟者中的肺癌是癌症死亡的第7至第9个主要原因。 在美国和其他国家，越来越多的从未吸烟者强调了理解该组肺癌的流行病学和生物学的重要性。 流行病学，分子和临床数据表明，吸烟者和非吸烟者的肺癌分子机制可能有所不同，这使得与吸烟者中的肺癌相比，从不吸烟者中的肺癌与肺癌不同。 从不吸烟者中肺癌的遗传流行病学尚未得到很好的探索，这很大程度上是因为在相关研究中遇到所需的样本量很难。我们提出了一个多中心（总共来自北美，以色列和欧洲的22个地点）全基因组范围的肺癌研究中的肺癌研究中的肺癌研究以下具有以下特定目标：目标1：发现阶段：识别候选SNP，影响从未吸烟的肺癌风险。该阶段将包括1553个从未吸烟的肺癌病例和1553个对照组匹配的年龄，性别和研究地点。目标2：复制阶段：使用一组独立的病例和国际肺癌财团（ILCCO）研究的独立病例和对照进行复制分析。在此阶段，将有1581个独立案例和1581个匹配的对照。目标3：识别和探索与肺癌的风险相关的途径。探索基因基因和基因环境相互作用对永不吸烟者肺癌风险的影响。 这将是第一个旨在确定白种人从未吸烟的肺癌易感性的GWA。我们将结合来自多个站点的可用资源，以实现足以本研究的样本量。该研究将确定对永无吸烟者肺癌易感性的遗传结构。