Exploring somatic mutations in human tissue (IRAS 363050)

Cancer can develop when DNA changes build up in our cells over time, but we still do not fully understand why it affects people differently across ages, organs and parts of the world. We will examine DNA changes in healthy and cancerous tissues from children and adults around the globe, using DNA sequencing to uncover patterns that reveal how mutations arise. By comparing different tissues, age groups and populations, we can better understand what drives cancer risk. Our findings could help improve cancer prevention and deepen our understanding of how cancer develops.

Cancer develops through the accumulation of somatic mutations in DNA, but the factors that influence mutation patterns across tissues, populations and age groups remain incompletely understood. This work will examine the number and types of somatic mutations in normal and cancerous tissues, with a particular focus on cancers of the gastrointestinal and urinary systems. Samples will be derived from children and adults of different ages and from populations worldwide.

Using DNA sequencing, we will identify mutational signatures that provide insight into the biological processes responsible for mutation accumulation and cancer development. By comparing tissues, age groups and geographic populations, we aim to understand why some tissues are more susceptible to mutations and why cancer incidence varies across regions and generations. The study will use only existing anonymised tissue, blood, urine and stool samples provided by international collaborators under appropriate ethical approvals. Findings will improve understanding of the mechanisms underlying cancer development and may inform future prevention strategies.

Rationale

Cancer develops through the accumulation of somatic mutations, but the processes that drive these changes and explain differences between tissues, ages, and populations remain poorly understood. International variation in cancer incidence suggests that many cases are linked to environmental or lifestyle exposures and may be
preventable.

By sequencing normal and cancerous tissues from the gastrointestinal and urinary systems, this study will characterise mutation burden and patterns, identify cancer-causing changes, and compare mutational processes across populations and age groups. The findings will fill key gaps in understanding why some cancers are rising in younger people and why rates vary globally, providing evidence to inform future prevention strategies.

Aims

The study aims to:

• understand how somatic mutations arise and accumulate in normal and cancerous tissues of the gastrointestinal and urinary systems, and how these changes contribute to cancer
  development and variation in cancer risk
• investigate how mutational patterns differ across populations and exposures, how mutation burden varies with age including in younger patients, and whether certain tissues are more vulnerable to specific mutational processes

Primary Outcome

The primary outcomes are to generate a register of somatic mutations in normal and diseased tissues of the gastrointestinal and urinary systems, and to compare these mutations across geographic regions, age groups (including children and adults), and between healthy individuals and those with disease states such as cancer

Key Secondary outcome(s)

None

Study Type

Observational

Participant and Sample Information

Populations involved:

Individuals with cancer, plus healthy controls.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

8500

Key inclusion criteria:

• Existing human samples collected under appropriate consent and ethical approval.
• Tissue biopsies from the gastrointestinal tract and urinary tract.
• Blood, urine, stool, and DNA extracted from these sample types.
• Samples from both cancerous and non-cancerous tissues.
• Samples from adults and children across a range of ages and populations.
• Samples provided only in anonymised or pseudonymised form.

Key exclusion criteria:

Anything outside of the above and samples where there is no consent and/or ethical approval for use in research.

Recruitment status:

Non-recruiting: Pre-collected samples only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the West of Scotland REC 4 NHS Research Ethics Committee. The study received REC approval on 2 October 2025.

IRAS 363050

REC reference: 25/WS/0154

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date 

Ongoing

Further Information

For enquiries about the scientific aims of this study or potential collaboration, please contact the relevant scientific programme at mrs@sanger.ac.uk.

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.