Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers

Oncotarget. 2015 Nov 24;6(37):39855-64. doi: 10.18632/oncotarget.5627.

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.

Keywords: SNP; pancreatic cancer; rs488087.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Base Sequence
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Lipase / genetics*
  • Male
  • Middle Aged
  • Minisatellite Repeats / genetics
  • Odds Ratio
  • Pancreatic Neoplasms / genetics*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Risk Factors
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • KRAS protein, human
  • CEL protein, human
  • Lipase
  • Proto-Oncogene Proteins p21(ras)