Characteristics and Risk Factors for Lung Cancer in Never-smokers in Australia and China

Lung cancer is the leading cause of cancer death globally, including Australia and China. Although tobacco smoke is the major cause of lung cancer, 15-25% of global lung cancer cases occur in lifelong never-smokers. Lung cancer in never-smokers (LCINS), when considered as a distinct entity, was ranked as the 7th leading cause of cancer death worldwide in 2000, but there is still limited understanding of its aetiology. Although the International Agency for Research on Cancer identified multiple agents other than smoking to be lung carcinogens in humans, a significant portion of lung cancer patients have not been exposed to them, suggesting that other risk factors remain to be established. To establish a clear link between a risk factor and LCINS, it is important to focus on studies with exclusive or subgroup analyses of never-smokers, as LCINS has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. The aim of this thesis is to examine the roles of many potential risk factors for lung cancer among never-smoker groups using various datasets including the 45 and Up Study and China Kadoorie Biobank, the largest prospective cohort in Australia and China respectively. This thesis is in seven chapters: an introduction, two review and three original research articles in the format of peer-reviewed publications, and a final discussion. It has provided risk estimates for several risk factors including residential radon, Asian country of birth, household air pollution and certain female hormonal factors (duration of oral contraceptive use, number of livebirths and time since menopause), and added valuable new evidence to the aetiology of LCINS. It also provides better understanding of other risk factors associated with LCINS, brings awareness to the significant cancer burden attributed to LCINS and highlights the important public health implications for the prevention and early detection of lung cancer among never-smokers