Ancestral susceptibility to colorectal cancer

0373767 - ÚEM 2013 RIV GB eng J - Journal Article
Huhn, S. - Pardini, Barbara - Naccarati, Alessio - Vodička, Pavel (ed.) - Hemminki, K. - Försti, A.
Ancestral susceptibility to colorectal cancer.
Mutagenesis. Roč. 27, č. 2 (2012), s. 197-204. ISSN 0267-8357. E-ISSN 1464-3804
R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286
Grant - others:EU FP7(XE) HEALTH-F4-2007-200767
Institutional research plan: CEZ:AV0Z50390512
Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.500, year: 2012

Several studies have shown that susceptibility to complex diseases can be mediated by ancestral alleles. Using RNAi screening, CTNNBL1 was identified as a putative regulator of the Wnt signaling pathway, which plays a key role in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in CTNNBL1 have been associated with obesity, a known risk factor for CRC. We investigated whether genetic variation in CTNNBL1 affects susceptibility to CRC and tested for signals of recent selection. In the Czech cohort, containing sporadic cases, the ancestral alleles of three SNPs showed evidence of association with CRC: rs2344481 (OR 1.44, 95%CI 1.06-1.95, dominant model), rs2281148 (OR 0.59, 95%CI 0.36-0.96, dominant model) and rs2235460 (OR 1.38, 95%CI 1.01-1.89, AA vs. GG). Data derived from several databases and statistical tests consistently pointed to a likely shaping of CTNNBL1 by positive selection.
Permanent Link: http://hdl.handle.net/11104/0206836