title: Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk.
abstract: To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's χ(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P<0.0001) cumulative effect of the at-risk alleles or genotypes with OR at 1.62 (CI: 1.10-2.37), 2.09 (CI: 1.43-3.07), 2.87 (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at-risk alleles, respectively, and OR at 1.71 (CI: 1.18-2.46), 2.29 (CI: 1.55-3.38) and 6.21 (CI: 2.67-14.42) for 1, 2 and 3 at-risk genotypes, respectively. Combination of SNPs may therefore explain a fraction of clinical situations suggestive of an increased risk for CRC.
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Department of Genetics, University Hospital, Rouen, France.|Cancéropôle Nord-Ouest, France.
authors: Stéphanie
authors: S
authors: Baert-Desurmont
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Department of Genetics, University Hospital, Rouen, France.|Cancéropôle Nord-Ouest, France.
authors: Françoise
authors: F
authors: Charbonnier
authors: Department of Biostatistics, University Hospital and Inserm U657, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Centre d'Investigation Clinique, University Hospital, Rouen, France.
authors: Estelle
authors: E
authors: Houivet
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Cancéropôle Nord-Ouest, France.
authors: Lorena
authors: L
authors: Ippolito
authors: Department of Genetics, University Hospital, Rouen, France.
authors: Jacques
authors: J
authors: Mauillon
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors: Marion
authors: M
authors: Bougeard
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Department of Genetics, Comprehensive Cancer Center Eugène Marquis, Rennes, France.
authors: Caroline
authors: C
authors: Abadie
authors: Department of Genetics, Institut Gustave Roussy, Villejuif, France.
authors: David
authors: D
authors: Malka
authors: Department of Genetics, Comprehensive Cancer Center Val d'Aurelle, Montpellier, France.
authors: Jacqueline
authors: J
authors: Duffour
authors: Department of Genetics, Comprehensive Cancer Center Léon Bérard, Lyon, France.
authors: Françoise
authors: F
authors: Desseigne
authors: Department of Genetics, AP-HP, Hôpital Saint Antoine, Paris, France.
authors: Chrystelle
authors: C
authors: Colas
authors: Department of Genetics, University Hospital, Montpellier, France.
authors: Pascal
authors: P
authors: Pujol
authors: Department of Genetics, University Hospital, Lille, France.
authors: Sophie
authors: S
authors: Lejeune
authors: Department of Genetics, Comprehensive Cancer Center Eugène Marquis, Rennes, France.
authors: Catherine
authors: C
authors: Dugast
authors: Department of Genetics, Institut Curie, Paris, France.
authors: Bruno
authors: B
authors: Buecher
authors: Department of Genetics, University Hospital and Comprehensive Cancer Center Georges-François Leclerc, Dijon, France.
authors: Laurence
authors: L
authors: Faivre
authors: Department of Genetics, University Hospital, Grenoble, France.
authors: Dominique
authors: D
authors: Leroux
authors: Department of Genetics, Hospital, Niort, France.
authors: Paul
authors: P
authors: Gesta
authors: Department of Genetics, University Hospital, Montpellier, France.
authors: Isabelle
authors: I
authors: Coupier
authors: Department of Genetics, Comprehensive Cancer Center Claudius Regaud, Toulouse, France.
authors: Rosine
authors: R
authors: Guimbaud
authors: Department of Genetics, Comprehensive Cancer Center François Baclesse, Caen, France.
authors: Pascaline
authors: P
authors: Berthet
authors: Department of Genetics, University Hospital, Lille, France.
authors: Sylvie
authors: S
authors: Manouvrier
authors: Department of Genetics, University Hospital, Nantes, France.
authors: Estelle
authors: E
authors: Cauchin
authors: Department of Genetics, University Hospital, Saint Etienne, France.
authors: Fabienne
authors: F
authors: Prieur
authors: Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France.
authors: Pierre
authors: P
authors: Laurent-Puig
authors: Department of Genetics, University Hospital, Saint Etienne, France.
authors: Marine
authors: M
authors: Lebrun
authors: Department of Genetics, University Hospital, Nancy, France.
authors: Philippe
authors: P
authors: Jonveaux
authors: Department of Genetics, University Hospital, Nîmes, France.
authors: Jean
authors: J
authors: Chiesa
authors: Department of Genetics, Institut Gustave Roussy, Villejuif, France.
authors: Olivier
authors: O
authors: Caron
authors: Department of Genetics, University Hospital, Angers, France.
authors: Marie-Emmanuelle
authors: ME
authors: Morin-Meschin
authors: Department of Genetics, Comprehensive Cancer Center François Baclesse, Caen, France.
authors: Florence
authors: F
authors: Polycarpe-Osaer
authors: Department of Genetics, University Hospital Edouard Herriot, Lyon, France.
authors: Sophie
authors: S
authors: Giraud
authors: Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France.
authors: Aziz
authors: A
authors: Zaanan
authors: Department of Genetics, University Hospital, Toulouse, France.
authors: Delphine
authors: D
authors: Bonnet
authors: Department of Genetics, University Hospital, Nancy, France.
authors: Ludovic
authors: L
authors: Mansuy
authors: Department of Genetics, Comprehensive Cancer Center Léon Bérard, Lyon, France.
authors: Valérie
authors: V
authors: Bonadona
authors: Department of Genetics, University Hospital and Comprehensive Cancer Center Georges-François Leclerc, Dijon, France.
authors: Salima
authors: S
authors: El Chehadeh
authors: Department of Genetics, Cancer Centre, Cliniques Universitaires St Luc, Bruxelles, Belgium.
authors: François
authors: F
authors: Duhoux
authors: Department of Genetics, Institut Curie, Paris, France.
authors: Marion
authors: M
authors: Gauthier-Villars
authors: Department of Gastroenterology, University Hospital Edouard Herriot, Lyon, France.
authors: Jean-Christophe
authors: JC
authors: Saurin
authors: Department of Genetics, University Hospital, Besançon, France.
authors: Marie-Agnès
authors: MA
authors: Collonge-Rame
authors: Department of Genetics, Institut Gustave Roussy, Villejuif, France.
authors: Laurence
authors: L
authors: Brugières
authors: Department of Genetics, Comprehensive Cancer Center Léon Bérard, Lyon, France.
authors: Qing
authors: Q
authors: Wang
authors: Department of Genetics, Institut Gustave Roussy, Villejuif, France.
authors: Brigitte
authors: B
authors: Bressac-de Paillerets
authors: Department of Genetics, University Hospital, Montpellier, France.
authors: Jean-Marc
authors: JM
authors: Rey
authors: Department of Genetics, Comprehensive Cancer Center Claudius Regaud, Toulouse, France.
authors: Christine
authors: C
authors: Toulas
authors: Molecular of Genetics, University Hospital, Lille, France.
authors: Marie-Pierre
authors: MP
authors: Buisine
authors: Department of Genetics, University Hospital, Nancy, France.
authors: Myriam
authors: M
authors: Bronner
authors: Department of Genetics, University Hospital, Nancy, France.
authors: Joanna
authors: J
authors: Sokolowska
authors: Department of Genetics, Comprehensive Cancer Center François Baclesse, Caen, France.
authors: Agnès
authors: A
authors: Hardouin
authors: Centre d'Investigation Clinique, University Hospital, Rouen, France.
authors: Anne-Françoise
authors: AF
authors: Cailleux
authors: Department of Clinical Research, University Hospital, Rouen, France.
authors: Hakim
authors: H
authors: Sebaoui
authors: Department of Clinical Research, University Hospital, Rouen, France.
authors: Julien
authors: J
authors: Blot
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Department of Genetics, University Hospital, Rouen, France.|Cancéropôle Nord-Ouest, France.
authors: Julie
authors: J
authors: Tinat
authors: Department of Biostatistics, University Hospital and Inserm U657, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors: Jacques
authors: J
authors: Benichou
authors: Inserm U1079, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.|Department of Genetics, University Hospital, Rouen, France.|Cancéropôle Nord-Ouest, France.
authors: Thierry
authors: T
authors: Frebourg
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15; D002887:Chromosomes, Human, Pair 18; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors