Epidemiology of Solid Tumour Progression

Our laboratory is studying the behaviour of cancers of the aerodigestive tract (esophageal cancer, head and neck cancer, lung cancer) as well as orphan thoracic tumours such as thymoma and mesothelioma. As a unique translational epidemiologic laboratory within MBP, we are focused on discovering novel molecularly-based methods for risk stratification, prognostication, and treatment of patients.

Genetic and environmental influences are interwoven into the fabric of cancer prognosis. Our laboratory performs human population-based research, using candidate gene approaches, pathway-based approaches, and high density SNP technology to identify the potential biologic pathways involved in esophageal cancer development. Discovery of putative pathways becomes the first step in narrowing the list of potential environmental carcinogens. We are currently developing customized high density SNP-chips for assessment in aerodigestive cancers, and collaborating with computational biologists on their analysis.

These same genetic and environmental factors can play critical roles in cancer behaviour after diagnosis,and in response to therapy. Our laboratory is studying pharmacogenomic factors in cancer treatment, both in terms of traditional chemotherapeutic agents as well as molecular targeted agents. We recently assessed the role of several functional polymorphic variants of EGFR in lung cancer patients treated with an EGFR-tyrosine kinase inhibitor, and found that these polymorphic variants predict survival and treatment response. Another focus in our laboratory is the assessment of putative serum biomarkers to help monitor patient therapy and response. In addition to human population studies, pre-clinical models of esophageal and gastric cancers are being developed in our laboratory. These resources are being used to assess genotype-phenotype correlations, testing of molecular targeted drugs and novel therapeutics, and for pre-clinical testing of biomarkers.

Currently, we are assessing biomarkers and genetic variations in biologic samples obtained from the following large scale studies: Lung Cancer Screening Study; Mesothelioma Screening Study; Molecular Epidemiology of Lung, Esophageal Cancer, Thymoma and Mesothelioma, a series of US-based studies of esophageal, lung and pancreatic cancer), and Head and Neck Cancers from PMH. In addition, our laboratory is involved in the biologic assessments of a number of Phase I/II/III cancer treatment studies. We are and have been CIHR, NCI (US), NCICCTG, and Doris Duke funded, with close collaborations with Harvard, Laval, and Seattle.

Graduate Students:

Selected References:

• Heist RS, Zhou W, Chirieac LR, Cogan-Drew T, Liu G, Su L, Neuberg D, Lynch TJ, Wain JC, Christiani DC. MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer. J Clin Oncol. 2007 Jun 1;25(16):2243-7.

• Liu G, Gurubhagavatula S, Zhou W, Wang Z, Yeap BY, Asomaning K, Su L, Heist R, Lynch TJ, Christiani DC. Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib. Pharmacogenomics J. 2007

• Liu G, Zhou W, Yeap BY, Su L, Wain JC, Poneros JM, Nishioka NS, Lynch TJ, Christiani DC. XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis. 2007 Jun;28(6):1254-8.

• Liu G, Zhou W, Christiani DC. Molecular epidemiology of nonsmall cell lung cancer. Semin Respir Crit Care Med. 2005 Jun;26(3):265-72.