Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers

Autor: Frédéric Fina, Dominique Figarella-Branger, Marc Bartoli, Françoise Silvy, Eric Mas, Dominique Lombardo, Emmanuelle Martinez, Fabrice Barlesi, René Laugier, Martin Krahn, Juan L. Iovanna, Mehdi Ouaissi
Přispěvatelé: Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d'Hepato-gastroentérologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MAS, Eric
Rok vydání: 2015
Předmět:
Adult
Male
medicine.medical_specialty
Pancreatic ductal adenocarcinoma
Adolescent
Genotype
pancreatic cancer
Population
SNP
[SDV.CAN]Life Sciences [q-bio]/Cancer
Single-nucleotide polymorphism
Minisatellite Repeats
rs488087
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Biology
Polymerase Chain Reaction
Polymorphism
Single Nucleotide
Proto-Oncogene Proteins p21(ras)
Young Adult
Gene Frequency
[SDV.CAN] Life Sciences [q-bio]/Cancer
Risk Factors
Pancreatic cancer
Odds Ratio
medicine
Humans
Point Mutation
Genetic Predisposition to Disease
Risk factor
education
Allele frequency
Alleles
Gynecology
education.field_of_study
Base Sequence
Pancreatic tissue
Lipase
Sequence Analysis
DNA
Middle Aged
medicine.disease
Molecular biology
3. Good health
Pancreatic Neoplasms
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Oncology
Female
Research Paper
Zdroj: Oncotarget
Oncotarget, Impact journals, 2015, 24 (6), pp.39855-39864. ⟨10.18632/oncotarget.5627⟩
Oncotarget, 2015, 24 (6), pp.39855-39864. ⟨10.18632/oncotarget.5627⟩
ISSN: 1949-2553
DOI: 10.18632/oncotarget.5627
Popis: // Emmanuelle Martinez 1, 2 , Francoise Silvy 1, 2 , Frederic Fina 1, 2, 3 , Marc Bartoli 4 , Martin Krahn 4, 5 , Fabrice Barlesi 1, 2, 6 , Dominique Figarella-Branger 1, 2, 7 , Juan Iovanna 8, 9, 10 , Rene Laugier 11 , Mehdi Ouaissi 1, 2, 12 , Dominique Lombardo 1, 2 , Eric Mas 1, 2 1 Aix-Marseille Universite, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France 2 INSERM, UMR_S 911, F-13005, Marseille, France 3 LBM- Assistance Publique Hopitaux de Marseille, Hopital Nord, Service de Transfert d’Oncologie Biologique, F-13015, Marseille, France 4 Aix-Marseille Universite, INSERM, UMR 910, F-13005, Marseille, France 5 Assistance Publique Hopitaux de Marseille, Hopital de la Timone-Enfants, Departement de Genetique Medicale, F-13005, Marseille, France 6 Assistance Publique Hopitaux de Marseille, Hopital Nord, Service d’Oncologie Multidisciplinaire & Innovation Therapeutique, F-13915, Marseille, France 7 Assistance Publique Hopitaux de Marseille, Hopital de la Timone, Service d’Anatomopathologie, F-13005, Marseille, France 8 Aix-Marseille Universite, CRCM, Centre de Recherche en Cancerologie de Marseille, F-13009, Marseille, France 9 INSERM, UMR_S 1068, F-13009, Marseille, France 10 CNRS, UMR 7258, F-13009, Marseille, France 11 Assistance Publique Hopitaux de Marseille, Hopital de la Timone, Service de Gastroenterologie, F-13005, Marseille, France 12 Assistance Publique Hopitaux de Marseille, Hopital de la Timone, Service de Chirurgie Digestive et Viscerale, F-13005, Marseille, France Correspondence to: Eric Mas, e-mail: eric.mas@univ-amu.fr Dominique Lombardo, e-mail: dominique.lombardo@univ-amu.fr Keywords: SNP, rs488087, pancreatic cancer Abbreviations: BSDL, bile-salt-dependent lipase; PDAC, pancreatic ductal adenocarcinoma; PC, pancreatic cancers Received: June 23, 2015 Accepted: October 05, 2015 Published: October 16, 2015 ABSTRACT Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present.
Databáze: OpenAIRE
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