Evidence for a colorectal cancer susceptibility locus on chromosome 3q21–q24 from a high-density SNP genome-wide linkage scan

• Published in: Human molecular genetics 2006-10, Vol.15 (19), p.2903-2910
• Main Authors: Kemp, Zoe, Carvajal-Carmona, Luis, Spain, Sarah, Barclay, Ella, Gorman, Margaret, Martin, Lynn, Jaeger, Emma, Brooks, Neil, Bishop, D. Timothy, Thomas, Huw, Tomlinson, Ian, Papaemmanuil, Elli, Webb, Emily, Sellick, Gabrielle S, Wood, Wendy, Evans, Gareth, Lucassen, Anneke, Maher, Eamonn R, Houlston, Richard S
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 3 - genetics; Classical genetics, quantitative genetics, hybrids; Colorectal Neoplasms - genetics; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Genes, Dominant; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Linkage Disequilibrium; Lod Score; Male; Medical sciences; Methods, theories and miscellaneous; Models, Genetic; Molecular and cellular biology; Pedigree; Polymorphism, Single Nucleotide; Risk Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddl231

To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10 204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21–q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.