Molecular Epidemiology of Colorectal Cancer

Colorectal cancer ranks among the leading causes of cancer incidence and mortality worldwide. Molecular epidemiology combines analysis of somatic and germline genetic alterations, epigenetic modifications and environmental influences to clarify risk, prognosis and therapeutic response. Foundational work defined three principal carcinogenic pathways: chromosomal instability, microsatellite instability and the CpG island methylator phenotype. More recent studies have integrated high-throughput sequencing, epigenetic profiling and lifestyle data to uncover how dietary patterns, tobacco, alcohol and the gut microbiome shape distinct molecular subtypes. It has become clear that somatic mutational signatures can link specific exposures, such as red meat consumption, to driver mutations in oncogenes and epigenetic regulators. Concurrently, analysis of immune cell infiltration within the tumour microenvironment has emerged as a robust prognostic indicator. Through molecular pathological epidemiology, researchers now aim to develop refined risk models, guide chemopreventive strategies and tailor screening protocols. While promising, widespread clinical implementation will require standardisation of assays, greater diversity in study populations and integration with public health frameworks.

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Molecular Epidemiology of Colorectal Cancer publication trend

The graph below shows the total number of articles in molecular epidemiology of colorectal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Microsatellite instability (MSI): Deficiency of DNA mismatch repair leading to length variations in repetitive microsatellite sequences.

CpG island methylator phenotype (CIMP): Widespread hypermethylation of CpG islands in gene promoters, resulting in transcriptional silencing.

Chromosomal instability (CIN): Large-scale gains or losses of chromosomal segments causing aneuploidy and structural rearrangements.

Mutational signature: Specific pattern of somatic DNA mutations that reflects distinct endogenous or exogenous mutagenic processes.

Molecular pathological epidemiology (MPE): Interdisciplinary field linking molecular characteristics of disease with epidemiological exposures and outcomes.

Tumour microenvironment: Complex milieu of cancer cells, immune infiltrates, stromal cells and extracellular matrix influencing tumour behaviour.

References

1. Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention. International Journal of Molecular Sciences (2013).
2. Lifestyle, Diet, and Colorectal Cancer Risk According to (Epi)genetic Instability: Current Evidence and Future Directions of Molecular Pathological Epidemiology. Current Colorectal Cancer Reports (2017).
3. Discovery and Features of an Alkylating Signature in Colorectal CancerAlkylating Mutational Signature and Colorectal Cancer. Cancer Discovery (2021).
4. Smoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways. British Journal of Cancer (2020).
5. Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer. British Journal of Cancer (2022).