University of Pittsburgh Cancer Institute (UPCI)

Early Detection, Risk Prediction, and Prevention

CT scanLung cancer remains the leading cause of cancer-related death with poor survival due to the late stage at which lung cancer is typically diagnosed. Given the clinical burden from lung cancer and the relatively favorable survival associated with early-stage lung cancer, identifying individuals at high risk for developing lung cancer, and improving early detection methods for lung cancer, are of important potential clinical benefit. In addition, smoking cessation and avoidance, and cancer chemoprevention strategies are being examined within the LCP, in collaboration with the Cancer Epidemiology and Prevention Program and the Biobehavioral Oncology Program.


Selected Publications

  • Chronic mucous hypersecretion (CMH) contributes to COPD exacerbations and increased risk for lung cancer. Because methylation of gene promoters in sputum has been shown to be associated with lung cancer risk, it was tested whether such methylation was more common in persons with CMH. Results showed that CMH was significantly associated with an overall increased number of methylated genes, with SULF2 methylation demonstrating the most consistent association. The association between SULF2 methylation and CMH was significantly increased in males but not in females, and the association between methylation and CMH was more pronounced among 139 male former smokers with persistent CMH compared to current smokers. These findings demonstrate that especially male former smokers with persistent CMH have markedly increased promoter methylation of lung cancer risk genes and potentially could be at increased risk for lung cancer. (Bruse et. al., Respir Res. 2014 Jan 9;15:2.)
  • LCP researchers identified a panel of 10 serum biomarkers (prolactin, transthyretin, thrombospondin-1, E-selectin, C-C motif chemokine 5, macrophage migration inhibitory factor, plasminogen activator inhibitor, receptor tyrosine-protein kinase, erbb-2, cytokeratin fragment 21.1, and serum amyloid A) that distinguished lung cancer patients from controls with 77.1% sensitivity/76.2% specificity in cross-validation in the expanded training set, 73.3% sensitivity/93.3% specificity (balanced accuracy 83.3%) in the blinded verification set with the best discriminative performance in stage I/II cases: 85% sensitivity (balanced accuracy 89.2%). Importantly, the rate of misclassification of CT-screened controls was not different in most control subgroups with or without airflow obstruction or emphysema or pulmonary nodules. These biomarkers have potential to aid in the early detection of lung cancer and more accurate interpretation of indeterminate pulmonary nodules detected by CT screening. (Bigbee et. al., J Thorac Oncol. 2012 Apr;7(4):698-708.)
  • As computed tomography (CT) screening for lung cancer becomes more widespread, volumetric analyses, including doubling times, of CT-screen detected lung nodules and lung cancers may provide useful information in the follow-up and management of CT-detected lung nodules and cancers. Results indicated that volumetric analysis of CT-detected lung cancers is particularly useful in adenocarcinoma/bronchioloalveolar carcinoma. Prevalent cancers have a significantly slower doubling time than nonprevalent cancers and a higher percentage of adenocarcinoma/bronchioloalveolar carcinoma. These results should affect the management of indeterminant lung nodules detected on screening CT scans. (Wilson et. al., Am J Respir Crit Care Med. 2012 Jan 1;185(1):85-9.)

Members

Becich, Michael, MD, PhD
Biomedical Informatics (DBMI)
Kurland, Brenda, PhD
Biostatistics
Davison, Jon, MD
Pathology
Nason, Katie, MD
Surgery
Diergaarde, Brenda, PhD
Epidemiology
Ortiz, Luis, MD
Environmental & Occupational Health
Fuhrman, Carl, MD
Radiology
Schuchert, Matthew, MD
Cardiothoracic Surgery
Gopalakrishnan, Vanathi, PhD
Biomedical Informatics (DBMI)
Shapiro, Steven, MD
Medicine
Herman, James, MD
Medicine
Wilson, David, MD
Medicine
Huq, Mohammed Saiful, PhD
Radiation Oncology
Yousem, Samuel, MD
Pathology