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Journal Articles European Journal of Human Genetics Year : 2016

Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk

1 GMFC - Génétique du cancer et des maladies neuropsychiatriques
2 Service de génétique [Rouen]
3 Cancéropole Nord-Ouest
4 IRIB - Institute for Research and Innovation in Biomedicine
5 CIC Rouen - Centre d'Investigation Clinique [CHU Rouen]
6 CRLCC - CRLCC Eugène Marquis
7 IGR - Institut Gustave Roussy
8 CRLC Val d'Aurelle-Paul Lamarque
9 Centre Léon Bérard [Lyon]
10 CHU Saint-Antoine [AP-HP]
11 Service de génétique médicale [Montpellier]
12 Service de Génétique Médicale [Lille]
13 Service de génétique, Institut Curie Paris
14 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
15 Service de génétique médicale CHU Grenoble Hôpital Couple Enfant
16 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
17 Institut Claudius Regaud
18 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
19 Service de génétique médicale - Unité de génétique clinique [Nantes]
20 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
21 Service de Génétique [CHU HEGP]
22 Service de Génétique Clinique [CHRU Nancy]
23 Service de Génétique Clinique [CHRU Nïmes]
24 Service de génétique [Angers]
25 Hôpital Edouard Herriot [CHU - HCL]
26 Service Génétique Médicale [CHU Toulouse]
27 Service de génétique [Cliniques Universitaires Saint-Luc, Bruxelles]
28 Service d'Hépatologie et de Gastroentérologie [Lyon]
29 Génétique biologique histologie [CHRU de Besançon]
30 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
31 Unité de Recherche Clinique [CHU Rouen]
Rosine Guimbaud
  • Function : Author
  • PersonId : 955028
Pierre Laurent-Puig

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 chi(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.
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hal-01659109 , version 1 (04-03-2022)

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Stephanie Baert-Desurmont, Francoise Charbonnier, Estelle Houivet, Lorena Ippolito, Jacques Mauillon, et al.. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk. European Journal of Human Genetics, 2016, 24 (1), pp.99-105. ⟨10.1038/ejhg.2015.72⟩. ⟨hal-01659109⟩
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