Supervisors info:
Γαζούλη Μαρία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κοτσίνας Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ρουμπελάκη Μαρία, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Pancreatic ductal adenocarcinoma represents 90 % of pancreatic cancer and is
considered one of the deadliest malignancies in the 21st century. It is estimated to
become the second cause of cancer-associated mortality only behind lung cancer in a
few decades. Even if survival statistics have improved over the last decade through the
understanding of biological basis of disease and the improvement in clinical care, the
5-year survival rate remains very poor and does not exceed 12% while less than 20%
of patients survive for more than 1 year. The absence of straightforward, early
detection techniques contributes to the disease's late diagnosis and subsequently high
mortality since symptoms do not manifest until cancer has advanced and spread.
Pancreatic neuroendocrine tumors (PNETs) on the other hand, arise from
neuroendocrine cells in the pancreas, exhibiting slower growth and hormonal
hypersecretion compared to pancreatic ductal adenocarcinoma (PDAC). Despite their
rarity, PNETs display heterogeneity in histology and clinical behavior. Prognosis varies
based on factors such as tumor size, grade, and metastasis, with 5-year survival rates
ranging from 40% to 90%. Despite advancements in treatment, including surgery and
targeted therapies, challenges in managing PNETs persist, warranting ongoing research
efforts for improved outcomes.
The purpose of this study is to investigate the potent association of 3 single nucleotide
polymorphisms of Sirtuin 1 (SIRT1), a protein deacetylase involved in various cellular
processes including aging, metabolism, and tumorigenesis. The samples were
genotyped for the polymorphisms: rs3758391, rs144124002 and rs369274325.
Rs3758391 and rs144124002 polymorphisms were tested both in PDAC and PNET
patients, whereas rs369274325 was tested only in PDAC patients. Genotype frequency
comparison showed no association of rs144124002 with PDAC and PNET.
Rs369274325 polymorphism showed also no significant association with PDAC. In case
of rs3758391, there was a very strong association with PDAC, both in genotype and
allele level. Unfortunately, due to a small number of samples of PNET patients, no safe
conclusions could be extracted.
In conclusion, the rs3758391 polymorphism could serve as a potential biomarker for
pancreatic adenocarcinoma due to its strong association with the disease, as it was
shown at this study.
Keywords:
Sirtuins, Sirtuin 1, Pancreatic cancer, Polymorphisms
