CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early- and late-onset colorectal cancer

• Published in: Genes and immunity Vol. 12; no. 8; pp. 653 - 662
• Main Authors: Ågesen, T H, Berg, M, Clancy, T, Thiis-Evensen, E, Cekaite, L, Lind, G E, Nesland, J M, Bakka, A, Mala, T, Hauss, H J, Fetveit, T, Vatn, M H, Hovig, E, Nesbakken, A, Lothe, R A, Skotheim, R I
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2011; Nature Publishing Group
• Subjects: 631/208/199; 631/208/727/2000; 692/699/67/1504/1885; Adult; Age; Age of Onset; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cluster Analysis; Colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Disease prevention; Gastrointestinal surgery; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic aspects; Geriatrics; Glycoproteins - genetics; Glycoproteins - metabolism; Health risk assessment; Hospitals; Human Genetics; Humans; Immunity; Immunology; Informatics; Interferon; Lysophospholipase - genetics; Lysophospholipase - metabolism; Medical research; Middle Aged; Neoplasm Staging; original-article; Physiological aspects; Polymerase chain reaction; Receptor, Interferon alpha-beta - genetics; Receptor, Interferon alpha-beta - metabolism; Statistics; Tumors; Norway; genetic predisposition; hereditary cancer; gene expression microarray; colorectal neoplasm; early onset of disease
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2011.43

Colorectal cancer (CRC) incidence increases with age, and early onset of the disease is an indication of genetic predisposition, estimated to cause up to 30% of all cases. To identify genes associated with early-onset CRC, we investigated gene expression levels within a series of young patients with CRCs who are not known to carry any hereditary syndromes ( n =24; mean 43 years at diagnosis), and compared this with a series of CRCs from patients diagnosed at an older age ( n =17; mean 79 years). Two individual genes were found to be differentially expressed between the two groups, with statistical significance; CLC was higher and IFNAR1 was less expressed in early-onset CRCs. Furthermore, genes located at chromosome band 19q13 were found to be enriched significantly among the genes with higher expression in the early-onset samples, including CLC . An elevated immune content within the early-onset group was observed from the differentially expressed genes. By application of outlier statistics, H3F3A was identified as a top candidate gene for a subset of the early-onset CRCs. In conclusion, CLC and IFNAR1 were identified to be overall differentially expressed between early- and late-onset CRC, and are important in the development of early-onset CRC.