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CLINICAL AND GENETIC ASSOCIATIONS BETWEEN LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Dai, Jie (2018) CLINICAL AND GENETIC ASSOCIATIONS BETWEEN LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. PhD thesis, University of Sheffield.

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Abstract

Lung cancer and chronic obstructive pulmonary disease (COPD) are both leading causes of death in the world, and these two disease are closely linked in the clinical setting and at the genetic level. Previous studies have indicated that COPD confers a higher risk for development of lung cancer, and also affects prognosis once lung cancer has occurred. The present thesis further explored the influences of timing of COPD diagnosis, severity of airflow limitation, radiological emphysema, and genetic variants on lung cancer outcomes. Over 1,000 patients who were diagnosed with non-small cell lung cancer at Mayo Clinic were included. Near two-thirds of patients with COPD were underdiagnosed at the time of lung cancer diagnosis. In comparison to the previously recognized COPD, an incidentally diagnosed COPD was a major factor that increased risks of postoperative complications (incidental COPD versus non-COPD: 28.1% versus 16.5%, p<0.01) and impaired lung cancer survival (HR, 1.23; 95%CI, 1.05-1.45). Patients with moderate (HR, 1.22; 95%CI, 1.04-1.44) to severe airflow obstruction (HR, 1.75; 1.38-2.23) had a significantly poorer long-term outcome, while similar survival was found between patients with mild COPD and with normal lung function (p=0.97). The severity of regional emphysema was associated with overall survival in early stage lung cancer (p<0.01), which was independent of tumor location, and it was predictive of quality of life related to dyspnea after lung cancer treatment (p<0.05). Radiological emphysema was also correlated with postoperative lung function recovery (FEV1% and DLCO%, both p<0.05) when tumor resection was performed in the emphysematous region. Meta-analysis indicated that the negative impact of COPD was more pronounced in patients with non-small cell lung cancer (pooled HR, 1.23; 95%CI, 1.16-1.30), at an early-stage (pooled HR, 1.35; 95%CI, 1.12-1.63), and who received surgical treatment (pooled HR, 1.31; 95%CI, 1.13-1.51). The effects of single nucleotide polymorphisms on lung cancer survival differed by COPD status; SNP rs74798757 was significantly associated with survival from lung cancer with COPD, whereas SNP rs10218481, CASP7 rs17090907, GPC5 rs1409600 and rs163933, and TAAR8 rs8192627 were independent factors for survival in lung cancer patients who were COPD-free. These results indicate that COPD status may play a significant role in the association between genetic variants and lung cancer outcomes. Further validation from independent cohorts and functional characterization for these associations are necessary, which in future may benefit the COPD-lung cancer population.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Identification Number/EthosID: uk.bl.ethos.733631
Depositing User: Dr. Jie Dai
Date Deposited: 19 Feb 2018 10:02
Last Modified: 12 Oct 2018 09:51
URI: http://etheses.whiterose.ac.uk/id/eprint/19263

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