Titre du document / Document title

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

Auteur(s) / Author(s)

ColoRectal tumour Gene Identification (CoRGI) Study Consortium, ROYAUME-UNI
KEMP Zoe ⁽¹⁾ ; CARVAJAL-CARMONA Luis ⁽¹⁾ ; SPAIN Sarah ⁽¹⁾ ; BARCLAY Ella ⁽¹⁾ ; GORMAN Margaret ^{(1 2)} ; MARTIN Lynn ⁽¹⁾ ; JAEGER Emma ⁽¹⁾ ; BROOKS Neil ⁽³⁾ ; BISHOP D. Timothy ⁽⁴⁾ ; THOMAS Huw ⁽²⁾ ; TOMLINSON Ian ^{(1 2)} ; PAPAEMMANUIL Elli ⁽⁵⁾ ; WEBB Emily ⁽⁵⁾ ; SELLICK Gabrielle S. ⁽⁵⁾ ; WOOD Wendy ⁽⁵⁾ ; EVANS Gareth ⁽⁶⁾ ; LUCASSEN Anneke ⁽⁷⁾ ; MAHER Eamonn R. ⁽⁸⁾ ; HOULSTON Richard S. ⁽⁵⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Molecular and Population Genetics Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, ROYAUME-UNI
⁽²⁾ Colorectal Cancer Unit, Cancer Research UK, St Mark's Hospital, Watford Road, Harrow HA1 3UJ, ROYAUME-UNI
⁽³⁾ Bioinformatics, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, ROYAUME-UNI
⁽⁴⁾ Genetic Epidemiology Laboratory, Cancer Research UK, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, ROYAUME-UNI
⁽⁵⁾ Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, ROYAUME-UNI
⁽⁶⁾ Medical Genetics, St Mary's Hospital, Manchester, Hathersage Road, Manchester, M13 0JH, ROYAUME-UNI
⁽⁷⁾ Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton, SO16 5YA, ROYAUME-UNI
⁽⁸⁾ Section of Medical and Molecular Genetics, University of Birmingham School of Medicine and West Midlands Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, B15 2TG, ROYAUME-UNI

Résumé / Abstract

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.

Revue / Journal Title

Human molecular genetics   ISSN 0964-6906 

Source / Source

2006, vol. 15, n^o19, pp. 2903-2910 [8 page(s) (article)] (21 ref.)

Langue / Language

Anglais

Editeur / Publisher

Oxford University Press, Oxford, ROYAUME-UNI  (1992) (Revue)

Mots-clés anglais / English Keywords

Rectal disease ; Malignant tumor ; Intestinal disease ; Colonic disease ; Digestive diseases ; Colorectal cancer ; Genetics ; Genetic linkage ; Genome ; Single nucleotide polymorphism ; Density ; Genetic mapping ; Chromosome ; Sensitivity ;

Mots-clés français / French Keywords

Rectum pathologie ; Tumeur maligne ; Intestin pathologie ; Côlon pathologie ; Appareil digestif pathologie ; Cancer colorectal ; Génétique ; Liaison génétique ; Génome ; Polymorphisme mononucléotide ; Densité ; Carte génétique ; Chromosome ; Sensibilité ;

Mots-clés espagnols / Spanish Keywords

Recto patología ; Tumor maligno ; Intestino patología ; Colón patología ; Aparato digestivo patología ; Cancer de colon y recto ; Genética ; Ligamiento genético ; Genoma ; Polimorfismo mononucleótido ; Densidad ; Mapa genético ; Cromosoma ; Sensibilidad ;

Localisation / Location

INIST-CNRS, Cote INIST : 22540, 35400014299367.0070