Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers
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Emmanuelle Martinez1,2, Françoise Silvy1,2, Fréderic Fina1,2,3, Marc Bartoli4, Martin Krahn4,5, Fabrice Barlesi1,2,6, Dominique Figarella-Branger1,2,7, Juan Iovanna8,9,10, René Laugier11, Mehdi Ouaissi1,2,12, Dominique Lombardo1,2, Eric Mas1,2
1Aix-Marseille Université, CRO2, Centre de Recherche en Oncologie biologique et Oncopharmacologie, F-13005, Marseille, France
2INSERM, UMR_S 911, F-13005, Marseille, France
3LBM- Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Service de Transfert d’Oncologie Biologique, F-13015, Marseille, France
4Aix-Marseille Université, INSERM, UMR 910, F-13005, Marseille, France
5Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone-Enfants, Département de Génétique Médicale, F-13005, Marseille, France
6Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Service d’Oncologie Multidisciplinaire & Innovation Thérapeutique, F-13915, Marseille, France
7Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service d’Anatomopathologie, F-13005, Marseille, France
8Aix-Marseille Université, CRCM, Centre de Recherche en Cancérologie de Marseille, F-13009, Marseille, France
9INSERM, UMR_S 1068, F-13009, Marseille, France
10CNRS, UMR 7258, F-13009, Marseille, France
11Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service de Gastroentérologie, F-13005, Marseille, France
12Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Service de Chirurgie Digestive et Viscérale, F-13005, Marseille, France
Eric Mas, e-mail: [email protected]
Dominique Lombardo, e-mail: [email protected]
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
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.
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