Dataset Information

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 ?(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.

SUBMITTER: Baert-Desurmont S

PROVIDER: S-EPMC4795220 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Baert-Desurmont Stéphanie S Charbonnier Françoise F Houivet Estelle E Ippolito Lorena L Mauillon Jacques J Bougeard Marion M Abadie Caroline C Malka David D Duffour Jacqueline J Desseigne Françoise F Colas Chrystelle C Pujol Pascal P Lejeune Sophie S Dugast Catherine C Buecher Bruno B Faivre Laurence L Leroux Dominique D Gesta Paul P Coupier Isabelle I Guimbaud Rosine R Berthet Pascaline P Manouvrier Sylvie S Cauchin Estelle E Prieur Fabienne F Laurent-Puig Pierre P Lebrun Marine M Jonveaux Philippe P Chiesa Jean J Caron Olivier O Morin-Meschin Marie-Emmanuelle ME Polycarpe-Osaer Florence F Giraud Sophie S Zaanan Aziz A Bonnet Delphine D Mansuy Ludovic L Bonadona Valérie V El Chehadeh Salima S Duhoux François F Gauthier-Villars Marion M Saurin Jean-Christophe JC Collonge-Rame Marie-Agnès MA Brugières Laurence L Wang Qing Q Bressac-de Paillerets Brigitte B Rey Jean-Marc JM Toulas Christine C Buisine Marie-Pierre MP Bronner Myriam M Sokolowska Joanna J Hardouin Agnès A Cailleux Anne-Françoise AF Sebaoui Hakim H Blot Julien J Tinat Julie J Benichou Jacques J Frebourg Thierry T

European journal of human genetics : EJHG 20150415 1

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 ...[more]

PMID: 25873010

Similar Datasets

Project description:IntroductionInvasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism.Materials and methodsThe main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed.ConclusionThis trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS.Ethics and disseminationA Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication.Trial registration numberEudra-CT: 2019-000376-41 and NCT04238884; Pre-results.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets