Sökning: (WFRF:(Von Holst Susanna)) > (2012) > Cumulative impact o...
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000 | 05067naa a2200865 4500 | |
001 | oai:openarchive.ki.se:10616/41406 | |
003 | SwePub | |
008 | 240410s2012 | |||||||||||000 ||eng| | |
022 | a 1468-3288 | |
024 | 7 | a 10616/414062 hdl |
024 | 7 | a http://hdl.handle.net/10616/414062 URI |
024 | 7 | a https://doi.org/10.1136/gutjnl-2011-3005372 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Dunlop, Malcolm G4 aut |
245 | 1 0 | a Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations |
264 | c 2012-04-05 | |
264 | 1 | a Stockholm :b Karolinska Institutet, Dept of Molecular Medicine and Surgery,c 2012 |
338 | a electronic2 rdacarrier | |
520 | a OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance. | |
700 | 1 | a Tenesa, Albert4 aut |
700 | 1 | a Farrington, Susan M4 aut |
700 | 1 | a Ballereau, Stephane4 aut |
700 | 1 | a Brewster, David H4 aut |
700 | 1 | a Koessler, Thibaud4 aut |
700 | 1 | a Pharoah, Paul4 aut |
700 | 1 | a Schafmayer, Clemens4 aut |
700 | 1 | a Hampe, Jochen4 aut |
700 | 1 | a Voelzke, Henry4 aut |
700 | 1 | a Chang-Claude, Jenny4 aut |
700 | 1 | a Hoffmeister, Michael4 aut |
700 | 1 | a Brenner, Hermann4 aut |
700 | 1 | a von Holst, Susanna4 aut |
700 | 1 | a Picelli, Simone4 aut |
700 | 1 | a Lindblom, Annika4 aut |
700 | 1 | a Jenkins, Mark A4 aut |
700 | 1 | a Hopper, John L4 aut |
700 | 1 | a Casey, Graham4 aut |
700 | 1 | a Duggan, David J4 aut |
700 | 1 | a Newcomb, Polly A4 aut |
700 | 1 | a Abuli, Anna4 aut |
700 | 1 | a Bessa, Xavier4 aut |
700 | 1 | a Ruiz-Ponte, Clara4 aut |
700 | 1 | a Castellvi-Bel, Sergi4 aut |
700 | 1 | a Niittymaeki, Iina4 aut |
700 | 1 | a Tuupanen, Sari4 aut |
700 | 1 | a Karhu, Auli4 aut |
700 | 1 | a Aaltonen, Lauri A4 aut |
700 | 1 | a Zanke, Brent4 aut |
700 | 1 | a Hudson, Tom4 aut |
700 | 1 | a Gallinger, Steven4 aut |
700 | 1 | a Barclay, Ella4 aut |
700 | 1 | a Martin, Lynn4 aut |
700 | 1 | a Gorman, Maggie4 aut |
700 | 1 | a Carvajal-Carmona, Luis G4 aut |
700 | 1 | a Walther, Axel4 aut |
700 | 1 | a Kerr, David J4 aut |
700 | 1 | a Lubbe, Steven4 aut |
700 | 1 | a Broderick, Peter4 aut |
700 | 1 | a Chandler, Ian4 aut |
700 | 1 | a Pittman, Alan4 aut |
700 | 1 | a Penegar, Steven4 aut |
700 | 1 | a Campbell, Harry4 aut |
700 | 1 | a Tomlinson, Ian4 aut |
700 | 1 | a Houlston, Richard S4 aut |
710 | 2 | a Karolinska Institutet |
710 | 2 | a Karolinska Institutet |
773 | 0 | t Gutd Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgeryx 1468-3288x 0017-5749 |
856 | 4 | u http://hdl.handle.net/10616/41406x primaryx Object in contextx freey FULLTEXT |
856 | 4 | u https://europepmc.org/articles/pmc5105590?pdf=render |
856 | 4 8 | u http://hdl.handle.net/10616/41406 |
856 | 4 8 | u https://doi.org/10.1136/gutjnl-2011-300537 |
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