Association of a Genetic Variant in the Cyclin-Dependent Kinase Inhibitor ۲B with Risk of Pancreatic Cancer

Background: Pancreatic cancer (PC) is among the most aggressive tumors with a poor prognosis, indicating the need for the identification of a novel prognostic biomarker for risk stratifications. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome ۹p۲۱ associated with an increased risk of different malignancies. Methods: In the present study, we explore the possible relationship between genetic variant, rs۱۰۸۱۱۶۶۱, and gene expression of CDKN۲B in ۷۵ pancreatic cancer patients, and ۱۸۸ healthy individuals. DNAs were extracted and genotyping and gene expression were performed by TaqMan real-time PCR and RT-PCR, respectively. Logistic regression was used to assess the association between risk and genotypes, while the significant prognostic variables in the univariate analysis were included in multivariate analyses. Results: The patients with PDAC had a higher frequency of a TT genotype for rs۱۰۸۱۱۶۶۱ than the control group. Also, PDAC patients with dominant genetic model, (TT + TC), was associated with increased risk of developing PDAC (OR= ۱۴.۷۱, ۹۵% CI [۱.۹۶-۱۱۰.۳۵], p= ۰.۰۰۹). Moreover, patients with CC genotype had a higher expression of CDKN۲B, in comparison with TT genotype. Conclusions: Our findings demonstrated that CDKN۲A/B was associated with the risk of developing PDAC, supporting further investigations in the larger and multicenter setting to validate the potential value of this gene as an emerging marker for PDAC.

کلیدواژه ها:

CDKN۲A/B ، Rs۱۰۸۱۱۶۶۱ ، Pancreatic cancer ، Prognostic biomarker.