Comprehensive evaluation of the impact of 14 genetic variants on colorectal cancer phenotype and risk

Steven J. Lubbe, Maria Chiara Di Bernardo, Peter Broderick, Ian Chandler, Richard S. Houlston*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


To comprehensively evaluate the impact of recently identified colorectal cancer (CRC) variants at 1q41, 3q26.2, 8q23.3, 8q24.21, 10p14, 11q23.1, 12q13.13, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12.3, and 20q13.33 on risk and CRC phenotype, the authors analyzed 8,878 cases and 6,051 controls from the United Kingdom ascertained in 1999-2007. The impact of variants on the familial CRC risk was enumerated from age-, sex-, and calendar-specific CRC rates in the 50,924 first-degree relatives of cases. Each of the 14 susceptibility loci independently influences CRC with the risk increasing with increasing number of risk alleles carried (per allele odds ratio = 1.13; P = 2.99 × 10 -58) and, for those within the upper quintile, there is a 2.3-fold increased risk. In first-degree relatives of cases with ≤17, 18-21, and ≥22 risk alleles, standardized incidence ratios were 1.76, 2.08, and 2.25, respectively. Although the discriminatory attributes of the 14 CRC susceptibility loci for individual risk prediction are poor (area under the curve = 0.58), they may allow subgroups of the population at different CRC risks to be distinguished.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalAmerican journal of epidemiology
Issue number1
StatePublished - Jan 1 2012


  • colorectal neoplasms
  • genetic loci
  • genotype
  • polymorphism, single nucleotide
  • risk

ASJC Scopus subject areas

  • Epidemiology

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