Approved Research

M6A-associated genetic variants in pancreatic cancer and pre-cursor lesions, and associations with telomere maintenance and prognosis: a population-based study

Lay summary

Pancreatic cancer remains one of the deadliest cancers. Surgery may be the only curative treatment, but only a small minority with early-stage disease are eligible, confirming the need for earlier diagnosis and alternative therapies.

Although most people understand that our DNA (subunits of which are called chromosomes) contains the 'code' or genes to produce proteins that fulfil a particular function or need in the human body, many do not realize that the role of these genes can be changed by factors in our environment (both within and outside our bodies), so called 'epigenetics'. We intend to study the role that small genetic changes in the genes that code for some of the epigenetic regulators associated with pancreatic cancer initiation and progression have upon pancreatic cancer survival - we will study this among cancer patients, patients with conditions predisposing to cancer (cancer pre-cursors), and healthy patients. In addition, we intend to examine the length of the 'ends' of the chromosomes ('teleomeres'), of these patient groups. Telomeres these are like the plastic caps at the end of your laces which stop your thread (your chromosomes) from fraying, which would destroy our genetic information. We will determine if there are any associations between these genetic changes, telomere length and pancreatic cancer survival, as well as the relevance of these genetic variations to the prediction of pancreatic cancer. We expect work on the UK Biobank dataset will begin in early 2022 and end no later than mid-2024.

While the direct public health impact of this project will be minimal, any prospective findings could lead to additional research into the epigenetic regulation of pancreatic cancer and a potential therapeutic target (i.e., a METTL3 inhibitor) in the future. The downstream impact of this research could lead to a decrease in disease burden and mortality amongst the afflicted to the point where a diagnosis is no longer synonymous with death.