Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors

0430205 - ÚEM 2015 RIV NL eng J - Journal Article
Huhn, S. - Bevier, M. - Pardini, Barbara - Naccarati, Alessio - Vodičková, Ludmila - Novotný, J. - Vodička, Pavel - Hemminki, K. - Försti, A.
Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors.
Cancer Causes & Control. Roč. 25, č. 6 (2014), s. 759-769. ISSN 0957-5243. E-ISSN 1573-7225
R&D Projects: GA ČR(CZ) GAP304/12/1585; GA ČR GAP304/10/1286
Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1
Institutional support: RVO:68378041
Keywords : colorectal cancer * risk * survival
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.735, year: 2014

We hypothesized that germline variants in candidate cancer genes (CAN genes), may influence CRC risk, similar to APC. We analyzed 35 potentially functional single-nucleotide polymorphisms (SNPs) in 10 CAN genes (OBSCN, MLL3, PKHD1, SYNE1, ERCC6, FBXW7, EPHB6/TRPV6, ELAC1/SMAD4, EPHA3, and ADAMTSL3) using KBiosciences Competitive Allele-Specific PCRTM genotyping assays. In addition to CRC risk (1,399 CRC cases, 838 controls), we also considered the influence of the SNPs on patients’ survival (406 cases). Despite the suggested in silico functional relevance for the studied genes and SNPs, our data did not support a strong influence of the studied germline variants on CRC risk and survival. The strongest association with CRC risk and survival was found for MLL3 (rs6464211, OR 1.50, p = 0.002). Two SNPs in EPHB6/TRPV6 (dominant model) showed margine associations with survival (rs4987622 HR 0.58 p = 0.028 and rs6947538 HR 0.64, p = 0.036, respectively). Although somatic mutations in the CAN genes have been related to the development and progression of various types of cancers in several next-generation sequencing or expression analyses, our study suggests that the studied potentially functional germline variants are not likely to affect CRC risk or survival.
Permanent Link: http://hdl.handle.net/11104/0236435