AUG 21, 2013 08:00 AM PDT
Post Genome-Wide Association Studies
Presented at the Genetics and Genomics 2013 Virtual Event
105 46 2708

  • Associate Director for Population Sciences, Professor of Community and Family Medicine at the Geisel School of Medicine, Norris Cotton Cancer Center, Dartmouth College
      Dr. Amos moved in September, 2012 to the Geisel School of Medicine, where he is leading the Center for Genomic Medicine and serving as the Associate Cancer Center Director for Population Studies. Dr. Amos is leading studies to identify genetic risk factors for lung cancer and melanoma risk using genome-wide association and sequencing approaches. Dr. Amos leads a U19 grant entitled Transdisciplinary Research in Cancer of the Lung (TRICL) to identify genetic factors for lung cancer and interactions with smoking, study these factors in cell biological and animal models and to perform epidemiological studies of gene and environmental contributions to lung cancer risk. This grant includes 16 subcontracts and integrates work from an international consortium. Dr. Amos has served as the leader of the biostatistics core for the Genetic Epidemiology of Lung Cancer Consortium (GELCC) since its inception. With the move to Dartmouth he has replicated the computing environment that manages studies for GELCC and TRICL. Dr. Amos also provides direction for a grant that characterizes and sequences nicotinic receptors and uses fMRI to investigate effects of nicotinic receptor variants on responses to smoking cues. Dr. Amos has also worked extensively in the genetic epidemiology of colon cancer. He developed a Peutz-Jeghers syndrome registry while at M.D. Anderson Cancer Center. He has also studied genetic risk factors for sporadic colon cancer and hereditary nonpolyposis colon cancer. Dr. Amos has developed novel statistical approaches for gene-environment interaction analysis and for the identification of genes influencing complex diseases using either association based approaches or genetic linkage analysis.

    In this presentation I describe some of the approaches we are taking to identify the genetic architecture of common complex cancers with a particular focus on the etiology of lung cancer. Cancers results from joint effects of germline susceptibility along with common environmental exposures that propel risk for further stages of cancer development for some individuals. Genome-wide association studies have been highly effective in providing new insights into the etiology of these cancers. For lung cancer, genome-wide association analysis identified a key region of chromosome 15q that contains variants of nicotinic acetyl choline receptors that are expressed at low levels in most of the brain except a few selected areas, so these were not considered as primary candidates for smoking behavior nor for lung cancer risk. Further study of these loci shows they play a key role in lung cancer development as well as in tobacco use and smoking cessation. In particular, individuals with high risk variants have particular difficulty in tobacco cessation unless provided with pharmacological support. Other findings from genetic analysis of lung cancer have shown dramatic heterogeneity by histological subtype. A region on chromosome 5p21 harboring hTERT and CLPTM1L shows heterogeneity by histology, but animal models show that CLPTM1L plays a role in cancer progression. Finally, we discuss the role of sequencing for understanding the genetic architecture of cancers and how the limited resources available for genetic analysis might be applied for both sequencing and genome-wide assessment.

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