A NEW CLOCK IS RUNNING FOR MULTIPLE MYELOMA:
CIRCADIAN CLOCK PROTEIN-PERIOD 3 (PER-3)
POLYMORPHISM
Serin I.1,*, Pehlivan S.2, Demir I.3, Oyacı Y.2, Pehlivan M.3
*Corresponding Author: Istemi Serin, M.D., University of Health Sciences, Istanbul Training and
Research Hospital, Department of Hematology, Org. Nafiz GURMAN Cad., Fatih, 34098
tel.: +90 532 3172393, e-mail: serinistemi@hotmail.com
page: 37
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Abstract
Circadian Clock Protein PERIOD 3 (PER-3) is situated
on chromosome 1p36.23 and has a polymorphic domain
that expresses 4 or 5 copies of the 54-bp tandem repeat
sequence. PER-3 gene polymorphisms play a role in the
dysregulation of the immune system. This study intended
to investigate the distributions and clinical effectiveness of
the PER-3 gene polymorphism in multiple myeloma (MM)
patients. One hundred fifty patients diagnosed between January
2007-2009 and 100 healthy individuals were included
in this study. All patients were suitable for autologous stem
cell transplantation (ASCT) at first evaluation, and after 4
courses of VCD at least partial remission, ASCT was carried
out. Later, LD was used as maintenance. Genotypes of PER-
3 gene of patients and healthy controls were statistically
compared before treatment. In addition, these genotypes’
effects on overall and progression free survival (OS and
PFS) were investigated. Median PFS in the 5R/5R genotype
was found to be significantly longer, albeit low, at 86% (p
= 0.046). In the statistical analysis performed between the
4R/4R genotype and others, the PFS of patients with 4R/4R
was found to be significantly shorter at 40.4 months (p =
0.026). Patients with the 4R/4R genotype would have a risk
of 2.049 times of a shorter PFS (p=0.009). With this first
study investigating the effect of a circadian gene in MM,
the net effect of PER-3 gene polymorphism on PFS was
revealed, and it will be a guide for future studies.
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