Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers.
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.
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.
Emmanuelle
E
Martinez
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.
Françoise
F
Silvy
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.|LBM- Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Service de Transfert d'Oncologie Biologique, F-13015, Marseille, France.
Fréderic
F
Fina
Aix-Marseille Université, INSERM, UMR 910, F-13005, Marseille, France.
Marc
M
Bartoli
Aix-Marseille Université, INSERM, UMR 910, F-13005, Marseille, France.|Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone-Enfants, Département de Génétique Médicale, F-13005, Marseille, France.
Martin
M
Krahn
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.|Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Service d'Oncologie Multidisciplinaire & Innovation Thérapeutique, F-13915, Marseille, France.
Fabrice
F
Barlesi
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.|Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service d'Anatomopathologie, F-13005, Marseille, France.
Dominique
D
Figarella-Branger
Aix-Marseille Université, CRCM, Centre de Recherche en Cancérologie de Marseille, F-13009, Marseille, France.|INSERM, UMR_S 1068, F-13009, Marseille, France.|CNRS, UMR 7258, F-13009, Marseille, France.
Juan
J
Iovanna
Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service de Gastroentérologie, F-13005, Marseille, France.
René
R
Laugier
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.|Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service de Chirurgie Digestive et Viscérale, F-13005, Marseille, France.
Mehdi
M
Ouaissi
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.
Dominique
D
Lombardo
Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France.|INSERM, UMR_S 911, F-13005, Marseille, France.
Eric
E
Mas
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D055815:Young Adult
C117307:KRAS protein, human; C054621:CEL protein, human; D008049:Lipase; D016283:Proto-Oncogene Proteins p21(ras)
SNP; pancreatic cancer; rs488087