Evidence of linkage to chromosomes 10p15.3–p15.1, 14q24.3–q31.1 and 9q33.3–q34.3 in non-syndromic colorectal cancer families

• Published in: European journal of human genetics : EJHG Vol. 20; no. 1; pp. 91 - 96
• Main Authors: Saunders, Ian W, Ross, Jason, Macrae, Finlay, Young, Graeme P, Blanco, Ignacio, Brohede, Jesper, Brown, Glenn, Brookes, Diana, Lockett, Trevor, Molloy, Peter L, Moreno, Victor, Capella, Gabriel, Hannan, Garry N
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2012; Nature Publishing Group
• Subjects: Adenoma - diagnosis; Adenoma - epidemiology; Adenoma - genetics; Adult; Aged; Algorithms; Australia - epidemiology; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Chromosomes; Chromosomes, Human, Pair 10 - genetics; Chromosomes, Human, Pair 14 - genetics; Chromosomes, Human, Pair 9 - genetics; Classical genetics, quantitative genetics, hybrids; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Cytogenetics; Ethnic Groups - genetics; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Gene polymorphism; General aspects. Genetic counseling; Genes; Genes, Neoplasm; Genetic Linkage; Genetic Predisposition to Disease - genetics; Genetic Testing; Genetic variance; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genome-Wide Association Study; Genomes; Human; Human Genetics; Humans; Kruppel protein; Kruppel-Like Factor 6; Kruppel-Like Transcription Factors - genetics; Linkage analysis; Male; Medical genetics; Medical sciences; Middle Aged; Molecular and cellular biology; Mutation; Pedigree; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins - genetics; Risk Factors; Single-nucleotide polymorphism; Spain - epidemiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; Tumors; Australia; South Australia Australia; New South Wales Australia; Spain; 9q; 10p; colorectal cancer; linkage; 14q; Genetic mapping; Rectal disease; Family study; Pathogenesis; Colorectal cancer; Chromosome D14; Malignant tumor; Chromosome C10; Genetic determinism; Chromosome C9; Colonic disease; Genetic linkage; Digestive diseases; Intestinal disease; Genetics; Cancer
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2011.149

Up to 25% of colorectal cancer (CRC) may be caused by inherited genetic variants that have yet to be identified. Previous genome-wide linkage studies (GWLSs) have identified a new loci postulated to contain novel CRC risk genes amongst affected families carrying no identifiable mutations in any of the known susceptibility genes for familial CRC syndromes. To undertake a new GWLS, we recruited members from 54 non-syndromic families from Australia and Spain where at least two first-degree relatives were affected by CRC. We used single-nucleotide polymorphism arrays to genotype 98 concordant affected relative pairs that were informative for linkage analyses. We tested for genome-wide significance (GWS) for linkage to CRC using a quantile statistic method, and we found that GWS was achieved at the 5% level. Independently, using the PSEUDO gene-dropping algorithm, we also found that GWS for linkage to CRC was achieved ( P =0.02). Merlin non-parametric linkage analysis revealed significant linkage to CRC for chromosomal region 10p15.3–p15.1 and suggestive linkage to CRC for regions on 14q and 9q. The 10p15.3–p15.1 has not been reported to be linked to hereditary CRC in previous linkage studies, but this region does harbour the Kruppel-like factor 6 ( KLF6 ) gene that is known to be altered in common CRC. Further studies aimed at localising the responsible genes, and characterising their function will give insight into the factors responsible for susceptibility in such families, and perhaps shed further light on the mechanisms of CRC development.