Cancer is the leading cause of death in the UK, with lung cancer being the most common cause of cancer deaths worldwide. In the UK, survival is particularly poor for lung cancer compared to other European countries, which is partly due to cancers being diagnosed at later stages. This means that there is a big drive in the UK to diagnose lung cancer earlier, to improve survival.
Recently, we discovered a high platelet count in the blood was a risk marker of undiagnosed lung cancer in a CPRD study, and may be present before more serious symptoms develop. This has great potential to allow earlier diagnosis. There are several subtypes of lung cancer (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell lung cancer, and a smaller miscellaneous group), and it is not currently known whether a raised platelet count is more associated with a particular subtype. Therefore, the primary aim of this project will be to determine the association between raised platelet counts and a future diagnosis (within 12 months) of each particular subtype of lung cancer using statistical tests. This forms the first phase of a two-part study, where the results of phase one will inform and determine phase two. Phase two involves a laboratory investigation exploring the underlying mechanisms behind platelet count and the specific subtype(s) of lung cancer its associated with, determined by phase one.
This study will contribute to improving lung cancer diagnosis in a primary care setting and ultimately improve patient survival outcomes.
Thrombocytosis is a newly discovered risk marker of cancer. Our recent CPRD study (winning paper of the year) found that the one-year cancer incidence was 11.6% (95% CI 11.0 12.3) in males and 6.2% (95% CI 5.9 6.5) in females with thrombocytosis (1); far beyond the 3% risk threshold set by the National Institute for Health and Care Excellence (NICE) for urgent investigation for suspected cancer (2). Notably, lung cancer was the most common diagnosis associated with thrombocytosis. In this study, we aim to understand which histological sub-type of lung cancer (i.e. adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell lung cancer) is more strongly associated with it, which remains currently unknown.
This study forms the basis of this ISAC application, and it will utilise CPRD records linked to National Cancer Registration and Analysis Service (NCRAS) data and a matched cohort design (matched for age, gender, and practice) to determine which histological sub-type of lung cancer is most strongly linked to platelet count. This will form the basis for a second study (not to be conducted in the CPRD, but briefly described here) which involves an in vitro investigation of the biochemical nature of the signal released by the lung cancer cell subtype(s) identified in phase one that affect megakaryocyte physiology. We will only perform this phase on the histological subtypes identified in the CPRD study. Cell lines will be tested in vitro for their ability to promote megakaryocyte proliferation, differentiation and platelet formation in a co-culture system, using chromatographic fractionation, proteomics and classical biochemistry techniques to explore the mechanism(s) underlying the cancer-platelet association.
Together, this programme of work will contribute to identifying new ways to achieve earlier lung cancer diagnosis in primary care, and ultimately improve patient survival outcomes. It may also identify novel targets for biomarker development.
The primary outcome is platelet count before cancer diagnosis. Patients with primary lung cancer will be identified from CPRD records using a pre-defined list of medcodes that identify this cancer type. This will be their first cancer of any type; those with subsequent cancers diagnosed will be eligible for inclusion. Linked NCRAS data will be used to sub-categorise patients into four groups, based on the histological sub-type of their cancer: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell cancer.
Sarah Bailey - Chief Investigator - University of Exeter
Melissa Barlow - Corresponding Applicant - University of Exeter
Justin Matthews - Collaborator - University of Exeter
Luke Mounce - Collaborator - University of Exeter
William Hamilton - Collaborator - University of Exeter
NCRAS Cancer Registration Data