Counting alleles to predict recurrence of early-stage colorectal cancers

Lancet. 2002 Jan 19;359(9302):219-25. doi: 10.1016/S0140-6736(02)07448-2.


Background: Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. We used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers.

Methods: We studied 180 patients with no evidence of lymph-node or distant metastases at the time of surgery. DNA from paraffin-embedded tumours was tested for imbalances of chromosome 8p and 18q by digital SNP (single-nucleotide polymorphism)-a technique in which each allele in a sample is directly counted. Surviving patients had median follow-up of 68 months, and disease recurrence was used as the clinical endpoint.

Findings: Tumours were divided into three groups: "L" tumours (n=93) had allelic imbalances of chromosomes 8p and 18q, "L/R" tumours (n=60) had allelic imbalances of either chromosome 8p or 18q but not both, and "R" tumours (n=27) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% (95% CI 80-100) for patients with R tumours, 74% (61-87) for patients with L/R tumours, and 58% (47-69) for those with L tumours. These differences were significant (p<0.0001) and were independent of other variables--eg, Duke's stage A tumours of class L were much more likely to recur than Duke's stage B tumours of class R (p=0.002).

Interpretation: In patients without metastasis, allelic imbalance is a better predictor of prognosis than histopathological stage.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Allelic Imbalance*
  • Chromosomes, Human, Pair 18*
  • Chromosomes, Human, Pair 8*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Genetic Markers
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Survival Rate


  • Genetic Markers