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Dr. Chris Amos at the CIHR STAGE International Speaker Seminar Series
March 7, 2014 @ 12:00 pm - 1:00 pm
The CIHR STAGE International Speaker Seminar Series proudly presents
Dr. Chris Amos
Associate Cancer Center Director for Population Sciences
Head, Center for Genomic Medicine
Professor, Department of Community and Family Medicine
Geisel School of Medicine, Dartmouth College
Talk title: Genetic Architecture of Lung Cancer Susceptibility
Lung cancer is the leading cause of cancer mortality in Western societies but is the most heavily influenced by environmental exposures, and particularly from tobacco smoke. Despite the high environmental burden, family studies have shown strong evidence for genetic factors, similar in effect to other common cancers such as breast, lung, and colon cancers. To identify genetic factors for lung cancer we have been conducting family studies, large case-control analysis and sequencing. Familial studies have identified selected very high risk alleles for which gene-environment interactions play a significant contribution. Association studies have identified common alleles and show dramatic differences in genetic architecture of the major histological subsets. More recently, large scale imputation analysis identified uncommon alleles that have striking effects on lung cancer risk, suggesting additional uncommon variants with large effects remain to be identified by sequencing analysis. Finally, interpreting the effects that these alleles have on lung cancer development identified a new potential target for therapy and suggest that a more targeted approach to risk evaluation may assist in prevention.
My focus has been in the development and application of novel methods for understanding the basis of inherited predisposition to cancer and other complex diseases. I developed design criteria for the conduct of genetics studies and subsequently applied these for studying families and for population based analysis. I colead the international Genetic Associations and Mechanisms in Oncology (GAME-ON) consortium which brings together population-based researchers studying genetic and environmental causes of lung, breast, prostate, colon and ovarian cancers. Through application of genome-wide association study methods I have discovered novel variants that influence lung cancer risk. We identified a cluster of nicotinic receptor genes on chromosome 15q25.1 that commonly increase risk for lung cancer development and associate with increased nicotine dependence. Comparative studies showed an increase in risk of 30% per allele in Caucasians but a much higher risk of 80% per allele in African Americans. More recently, we identified a variant of BRCA2 that is associated with a 2.5 fold higher risk for squamous lung cancer. I am also a coleader of the Genetic Epidemiology of Lung Cancer Consortium that has targeted families that include multiple relatives affected with lung cancer and identified a locus on chromosome 6q, that predisposes individuals to have a high risk for lung cancer. We found that even light smoking greatly increases risk for lung cancer in these high risk families. Currently, my lab is heavily involved in the development and support of next-generation sequencing and other genomic applications at Dartmouth. We have worked closely with the Department of Pathology to assist in the development of clinical sequencing, which is now being routinely applied for most cancer sites presenting at Dartmouth. We are also very involved in sequencing for exploratory analyses to identify causes of a variety of cancers including lung, adrenal, breast, and colon cancers.