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Overview of the ECCE project

Over the past three decades, incidence rates of colorectal cancer in people younger than 50 years have doubled worldwide; about 10% of all new cases are now diagnosed in younger adults. This rising burden contrasts with decreasing rates in older adults, suggesting that new, as-yet unidentified, environmental or lifestyle factors may be driving disease in younger populations.

The ECCE project focuses on the gut microbiome as a potential key contributor. The microbiome is established early in life and is shaped by factors such as birth mode, diet, breastfeeding, and antibiotic exposure. Its composition varies across regions; in industrialized countries, it has higher levels of bacteria capable of producing DNA-damaging compounds.

The central hypothesis is that an increase in the prevalence of these mutagen-producing bacteria in the microbiomes of children over recent decades has led to higher mutational burdens in normal colorectal tissue early in life, ultimately contributing to the global rise in the incidence of early-onset colorectal cancer.

Specific aims of the ECCE project

  • Investigate whether early-life exposure to mutagen-producing bacteria contributes to the global rise in the incidence of early-onset colorectal cancer.
  • Identify and characterize microbiome-derived mutational signatures and other somatic mutational processes linked to early-onset colorectal cancer.
  • Study how these mutational processes arise and accumulate in normal colorectal tissue from childhood to adulthood.
  • Define temporal and geographical patterns of microbiome composition and associated mutational processes.
  • Integrate genomic, microbiome, and epidemiological data to assess associations with known risk factors for colorectal cancer (e.g. diet, metabolic disease).
  • Experimentally validate the mutagenic and carcinogenic potential of bacterial genotoxins using organoid and germ-free mouse models.
  • Characterize harmful microbial strains and community states associated with increased mutational burden.
  • Ultimately, aim to reduce the accumulation of mutations in normal colorectal epithelium and prevent the onset of early-onset colorectal cancer.

Long-term vision and expected impact

Incidence rates of colorectal cancer in individuals younger than 50 years have risen sharply over the past three decades in European countries and other high-income countries. This represents an urgent and growing public health challenge. Despite this alarming trend, its underlying causes remain largely unknown, limiting effective prevention strategies.

  • ECCE addresses this critical gap by testing the hypothesis that early-life exposure to mutagen-producing bacteria is a key driver of early-onset colorectal cancer. Building on converging biological and epidemiological evidence, the project will generate robust, population-scale data to directly evaluate causality.
  • Using state-of-the-art genomic, microbiome, and epidemiological approaches, ECCE will integrate unique international cohorts and biospecimens to identify microbial exposures, mutational processes, and modifiable risk factors across the life-course.
  • ECCE will provide the first comprehensive framework to link early-life microbial exposures with cancer development, enabling formal causal evaluation, including potential assessment through international expert bodies such as the IARC Monographs Programme.
  • Beyond advancing fundamental understanding, ECCE will deliver mechanistic insights that can underpin precision prevention strategies, early detection tools, and microbiome-targeted interventions.
  • Ultimately, ECCE aims to transform the prevention landscape for colorectal cancer, reduce the rising burden in young adults, and contribute to reversing the trends that are currently threatening future generations across Europe and globally.

Colorectal cancer around the world

Colorectal cancer, which affects the colon and rectum, is one of the most common and lethal cancers worldwide. There are striking geographical variations in incidence. Colorectal cancer is particularly common in high-income regions such as Europe, North America, Australia, and parts of East Asia, whereas it is less common in many regions of Africa, South America, and South-East Asia. Established risk factors include ageing, obesity, smoking, alcohol consumption, and certain dietary patterns. However, these factors do not fully explain the rapid rise in early-onset colorectal cancer observed in recent decades. This suggests that additional, as-yet unidentified, environmental and biological drivers are involved.

Early-onset colorectal cancer, typically defined as colorectal cancer diagnosed before age 50 years, has emerged as a major and concerning global public health trend over the past three decades. Unlike late-onset disease, early-onset colorectal cancer is increasing in incidence in many high-income countries, including in Europe, North America, and parts of Asia, while the underlying causes remain incompletely understood. Although traditional risk factors such as obesity, diet, alcohol consumption, and smoking may contribute, they do not fully explain the rapid and sustained rise in incidence in younger populations, suggesting the involvement of additional environmental, microbial, and early-life exposures. Clinically, early-onset colorectal cancer is often diagnosed at more advanced stages and can present with more aggressive disease characteristics, partly due to delayed recognition in younger individuals who are not considered to be at risk. This shifting epidemiology highlights an urgent need to identify novel causal mechanisms, improve early detection strategies, and develop targeted prevention approaches specifically addressing younger populations.

References

  1. Bray F, Colombet M, Mery L, Piñeros M, Znaor A, Zanetti R, et al., editors (2017). Cancer Incidence in Five Continents, Vol. XI (IARC Scientific Publication No. 166). Lyon: International Agency for Research on Cancer. https://publications.iarc.who.int/597
  2. World Cancer Research Fund (2026). Worldwide cancer data. https://www.wcrf.org/preventing-cancer/cancer-statistics/worldwide-cancer-data/
  3. Downham L, Laversanne M, Perdomo S, Filho AM, Bray F, Brennan P (2026). Increase of early-onset colorectal cancer: a cohort effect. J Natl Cancer Inst. 118(4):751–6. https://doi.org/10.1093/jnci/djaf238 PMID:40848248