Approved Research

Causal relationship between reduced kidney function and cancer risk: A Mendelian Randomisation study

Lay summary

Chronic kidney disease (CKD) is a major global health problem, involving reduced kidney function and affecting around 13% of the population. CKD is increasingly being identified as a risk factor for cancer and cancer death. Multiple mechanisms have been proposed to explain this observed association. However, the observational studies used to date have limitations that restrict their ability to establish causality, such as unmeasured confounding and reverse causation. This study will use Mendelian Randomisation to examine whether there is a causal relationship between reduced kidney function and the occurrence of cancer and cancer-related mortality.

We will use two data sources to conduct a Mendelian Randomisation study. We will identify genetic variants associated with CKD from the CKDGen consortium published meta-analysis of genome wide association studies. We then propose to use the UK Biobank dataset to investigate if these genetic variants are associated with an increased risk of cancer. If the genetic variants are associated with both CKD and cancer, then we can conclude that CKD is a causal risk factor for cancer. This is a valid conclusion given the design of the study, because genetic variants are randomly allocated at birth and not influenced by behavioural, socioeconomic or physiological factors.

This study aims to investigate the causal relationship between reduced kidney function and all-cause and site-specific cancer risk and death. Understanding if CKD is causally linked to cancer will inform the development of novel intervention strategies including screening for early detection and therapeutics to reduce the burden of cancer in the at-risk population.

We propose to complete this project in 24 months.