title: Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia.
abstract: The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernandez
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Dymerska
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Róża
authors.initials: R
authors.lastname: Derkacz
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sobieszczańska
authors.affiliation: Department of Surgery, Collegium Medicum, Nicolaus Copernicus University, Ulica Jagiellonska 13-15, 85-067 Bydgoszcz, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Banaszkiewicz
authors.affiliation: Asper Biotech, Vaksali 17a, 50410 Tartu, Estonia.
authors.forename: Hanno
authors.initials: H
authors.lastname: Roomere
authors.affiliation: Asper Biotech, Vaksali 17a, 50410 Tartu, Estonia.
authors.forename: Eneli
authors.initials: E
authors.lastname: Oitmaa
authors.affiliation: The Estonian Academy of Sciences, Kohtu 6, 10130 Tallinn, Estonia ; Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 23b-134, 51010 Tartu, Estonia ; Estonian Genome Centre of University of Tartu, Riia 23, 23b-134, 51010 Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Santariškiu g. 2, LT-08661 Vilnius, Lithuania ; State Research Institute, Innovative Medicine Center, Zygimantu 9, LT-01102 Vilnius, Lithuania.
authors.forename: Ramūnas
authors.initials: R
authors.lastname: Janavičius
authors.affiliation: State Research Institute, Innovative Medicine Center, Zygimantu 9, LT-01102 Vilnius, Lithuania.
authors.forename: Pavel
authors.initials: P
authors.lastname: Elsakov
authors.affiliation: Vilnius Maternity Hospital, Santariškiu g. 2, LT-08661 Vilnius, Lithuania.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Razumas
authors.affiliation: Institute of Oncology, Vilnius University, 21/27 M. K. Ciurlionio, LT-03101 Vilnius, Lithuania.
authors.forename: Kestutis
authors.initials: K
authors.lastname: Petrulis
authors.affiliation: Hereditary Cancer Center, Stradins University, Dzirciema 16 (Pardaugava), Riga LV-1007, Latvia ; Pauls Stradins Clinical University Hospital, Pilsonu 13, Riga LV-1002, Latvia.
authors.forename: Arvīds
authors.initials: A
authors.lastname: Irmejs
authors.affiliation: Hereditary Cancer Center, Stradins University, Dzirciema 16 (Pardaugava), Riga LV-1007, Latvia ; Pauls Stradins Clinical University Hospital, Pilsonu 13, Riga LV-1002, Latvia.
authors.forename: Edvīns
authors.initials: E
authors.lastname: Miklaševičs
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland ; Discipline of Medical Genetics, Faculty of Health, University of Newcastle and the Hunter Medical Research Institute, University Drive, Callaghan, NSW 2308, Australia ; Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Locked Bag 1000, New Lambton, NSW 2305, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Hereditary Cancer Center, Department of genetics and Pathology, Pomeranian Medical University, Ulica Polabska 4, 70-115 Szczecin, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński