Newsha Sardarzadeh1, Fatemeh Khojasteh-Leylakoohi2,3, Sedigheh Damavandi2, Ghazaleh Khalili-Tanha3,4, Mohammad Dashtiahangar2, Nima Khalili-Tanha2, Amir Avan2,3,4,5, Sakineh Amoueian6, Seyed Mahdi Hassanian2,3, Habibollah Esmaily2,3, Majid Khazaei2,3, Gordon Ferns7, Alireza Khooei6, Mohsen Aliakbarian1. 1. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Basic Medical Sciences Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Medical Genetics Research center, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 6. Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 7. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK.
Abstract
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 9p21 associated with an increased risk of different malignancies. Methods: In the present study, we explore the possible relationship between genetic variant, rs10811661, and gene expression of CDKN2B in 75 pancreatic cancer patients, and 188 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 rs10811661 than the control group. Also, PDAC patients with dominant genetic model, (TT + TC), was associated with increased risk of developing PDAC (OR= 14.71, 95% CI [1.96-110.35], p= 0.009). Moreover, patients with CC genotype had a higher expression of CDKN2B, in comparison with TT genotype. Conclusion: Our findings demonstrated that CDKN2A/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.
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 9p21 associated with an increased risk of different malignancies. Methods: In the present study, we explore the possible relationship between genetic variant, rs10811661, and gene expression of CDKN2B in 75 pancreatic cancer patients, and 188 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 rs10811661 than the control group. Also, PDAC patients with dominant genetic model, (TT + TC), was associated with increased risk of developing PDAC (OR= 14.71, 95% CI [1.96-110.35], p= 0.009). Moreover, patients with CC genotype had a higher expression of CDKN2B, in comparison with TT genotype. Conclusion: Our findings demonstrated that CDKN2A/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.
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