Cancers of the lung, head and neck, and pancreas are commonly diagnosed in the Canadian population. However, the prognosis for these cancers remains poor, with low 5-year survival rates for patients with pancreatic (7%) and lung (15%) cancers. There is a need to identify novel predictive and prognostic biomarkers that can serve as targets for prevention and treatment. Focusing on biomarkers that have both genetic and environmental determinants offers a promising avenue in this respect. Telomeres, which are structures that cap the ends of chromosomes, are an example of such a biomarker. Studies have linked variations in telomere length (TL) to cancer susceptibility and other aging-related diseases. Telomeres shorten with age and this can be accelerated by acitivites such as smoking and alcohol consumption. TL also has genetic determinants, and a number of studies have linked these variants with a higher risk of cancer, including lung and pancreatic cancers. However, the underlying biological mechanisms of these variants have not been fully elucidated and the prognostic value of TL and its genetic determinants has not been explored. Therefore, we propose to address these research gaps by investigating the comprehensive genetic profiles and TL with respect to both cancer etiology and progression. This project will use data from the Multicancer Case-control Study in Ontario, which recruited 3300 cancer cases (lung: 1500, head and neck: 1100, pancreas: 700) and 1500 age- and sex-matched controls and collected information on medical and family history, lifestyle factors and environmental exposures. The proposed dissertation work will augment the knowledge on the role of TL and its genetic determinants in cancer risk. Furthermore, it is novel in its aim to comprehensively investigate causal pathways related to TL for disease initiation and progression, and examine TL as a functional node combining the effects of genetic and environmental cancer risk factors.