title: Comprehensive evaluation of the impact of 14 genetic variants on colorectal cancer phenotype and risk.
abstract: 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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lubbe
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Di Bernardo
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Ian
authors.initials: I
authors.lastname: Chandler
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012306:Risk; D006113:United Kingdom