Metabolic determinants of cancer in the China Kadoorie Biobank

My DPhil work focuses on metabolic risk factors of cancer in the Chinese population, including adiposity, diabetes and physical inactivity. The Global Burden of Diseases Project estimated that metabolic risk factors accounted for 15.5% of attributable DALYs in 2015. Prospective studies in Western populations have shown that metabolic risk factors are associated with increased risk of certain cancers, such as pancreatic cancer and colorectal cancer. However, there is limited evidence from prospective studies in China.

I am working on the China Kadoorie Biobank, a prospective cohort study of 0.5 million people from 10 diverse regions. The outcomes of interest for my thesis include cancers of the gastrointestinal system, including pancreatic cancer, colorectal cancer, and liver cancer. We found that higher BMI levels were associated with higher risks of pancreatic cancer and colorectal cancer, but not with liver cancer.

 Figure 1: Adjusted hazard ratios (HRs) for cancer by BMI. BMI were classified as <20.0, 20.0-22.4 (reference), 22.5-24.9, 25.0-26.9, and ≥27.0 kg/m2. The sizes of the boxes are proportional to the inverse of the variance of the log hazard ratios. The analyses were stratified by age at risk, sex and study area, and adjusted for education, smoking, and alcohol. Numerical values above the 95%CI represent the hazard ratio and values beneath the 95%CI represent the number of cancer cases in each group.

Patients with diabetes had higher risks of developing pancreatic cancer and liver cancer, while higher random plasma glucose levels were associated with higher risks of all three cancers among participants without diabetes. We also found that higher levels of physical activity were associated with a lower risk of liver cancer.

 Figure 2. Adjusted hazard ratios (HRs) for cancer by diabetes and plasma glucose levels. Black boxes represent the HRs for random plasma glucose and the open box represents previously diagnosed diabetes. Random plasma glucose levels for participants without previously diagnosed diabetes at baseline were classified as ≤5.5 (reference), 5.6-6.7, 6.8-7.7, and ≥7.8 mmol/L.

Our findings for the associations of obesity and diabetes with risk of pancreatic cancer are in line with previous evidence in Western countries and other East Asian countries. There are at least fifty prospective studies on this topic, and they have been reviewed in two papers, one under review and one which has been published in the International Journal of Cancer.  A recent Mendelian randomisation study has suggested a causal role of fasting insulin in pancreatic cancer aetiology. In addition to the above-mentioned analyses, I am closely involved in an ongoing case-cohort study (700 PC cases and 1000 health sub-cohort members) that measured metabolomics and proteomics (i.e. circulating small molecules and proteins), which will provide valuable insights into the aetiology and inform early diagnosis of pancreatic cancer.

Yuanjie Pang joined the Clinical Trial Service Unit and Epidemiological Studies Unit in 2015. She holds a ScM in Epidemiology from Johns Hopkins University Bloomberg School of Public Health and an MBBs from Peking University Health Science Center. She is coming towards the end of her second year of her DPhil and her research involves investigating metabolic risk factors (adiposity, diabetes and physical activity) and cancer in the China Kadoorie Biobank.