Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Pancreatic cancer (PC) is often diagnosed late, limiting treatment options and survival.
• Identifying individuals at higher risk is crucial for early detection and prevention strategies.
• The bile salt-dependent lipase (BSDL) gene, particularly its variable number of tandem repeat (VNTR) regions, is implicated in pancreatic diseases.

Purpose of the Study:

• To investigate a potential genetic link between mutations in BSDL VNTR loci and predisposition to pancreatic cancer.
• To identify specific genetic markers that can define populations at increased risk for PC development.

Main Methods:

• Genomic DNA from a French patient cohort (PC patients and controls) was used.
• Touchdown-PCR amplified BSDL VNTR, followed by Sanger sequencing.
• Droplet digital PCR (ddPCR) with specific probes was developed to distinguish genotypes.

Main Results:

• The c.1719C > T transition (SNP rs488087) in BSDL VNTR was significantly more frequent in PC patients (63.90%) than in controls (27.30%).
• The T allele at rs488087 showed a high odds ratio of 4.7, suggesting a strong association with PC risk.
• Preliminary data indicate the germline T allele may promote Kras G12R/G12D somatic mutations, which are associated with poor prognosis.

Conclusions:

• The T allele of BSDL SNP rs488087 is a potential marker for identifying individuals at risk of developing pancreatic cancer.
• Routine screening for this genetic marker could facilitate earlier diagnosis and more intensive monitoring of at-risk individuals.
• Further research is warranted to validate these findings and explore the mechanistic link between the BSDL T allele and PC pathogenesis.