A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism

		Multiple Myeloma		Control	Control	p
		median	n^a (%)	median	n^b (%)
Age		56 (32-70)		53 (28-68)		0.140*
Gender	Female/Male		77/73 (51.3/48.7)		55/45 (55/45)	0.367^&
MM Subtypes	κ/λ		83/39 (68/32)
	G/A		79/18 (65/15)
	Light chain		25 (20)
Stage (Durie-Salmon)	II/III		38/84 (25/75)
	A/B		91/31 (79/21)
IPI	I		39 (32)
	II/III		34/50 (28/40)
ECOG	>1		12 (10)
Hemoglobin	gr/dL	10.4 (6.2-15)
Leukocyte	mm³	7200 (2760-18500)
Platelet	10³μL	172 (69-406)
C-reactive protein	mg/dL	8 (2.1-352)
LDH	IU/L	212 (93-1037)
B2-microglobulin	mg/L	4.9 (1.5-48)
Albumin	gr/L	3.5 (1.6-5.1)
Treatment	VCD, ASCT, LD
OS (10-years, %)		(79)
PFS (10-years, %)		(47) – 52.7 months
Relapse			63 (42)
Mortality			23 (15.3)
Follow-up duration, months, (range)		36.1 (4.1-155.2)

{ label (or @symbol) needed for fn[@id='j_bjmg-2022-0026_t1fn1'] } n^a = 150;

{ label (or @symbol) needed for fn[@id='j_bjmg-2022-0026_t1fn2'] } n^b = 100;

* median test,

& Pearson Chi-Square

**MM: Multiple myeloma, IPI:International Prognostic Index, ECOG:Eastern Cooperative Oncology Group, CRP:C-reactive protein, LDH: Lactate dehydrogenase, OS: Overall survival, PFS: Progression free survival, VCD: Bortezomib-cyclophosphamide and dexamethasone, LD: Lenalidomide- dexamethasone, ASCT: Autologous stem cell transplantation

Table 2.

Comparison of frequencies of PER-3 gene variants between patients with MM and healthy controls

PER3	Genotype	Multiple Myeloma	Healthy Controls	OR Exp(B)	95% CI	p
Genotypes		n=^a (%)	n=100 (%)
PER-3	4R/4R	70 (46.7)	42 (42)	0.657*	0.285-1.517*	0.325*
	4R/5R	64 (43.3)	44 (44)	0.745*	0.320-1.734*	0.494*
	5R/5R	16 (10.7)	14 (14)	1.363^&	0.633-2.935^&	0.434^&
Allele
	4R	204 (67.5)	128 (64)
	5R	98 (32.5)	72 (36)	1.159^&	0.796-1.689^&	0.443^&

a n= 150,

* :OR (95%CI) was adjusted by age and sex,

& Fisher’s Exact Test.

PER3: Circadian Clock Protein PERIOD 3

Table 3.

Comparison of PFS and OS with prognostic factors of patients with MM

			PFS*	Log Rank p-value	os*,^#	Log Rank p
		n	52.7		77^#
Gender, n	Female / Male	73/77	89.3 /39.2	0.080	66^# / 69^#	0.690
Age, n	<65 / >65	130/20	54.3 / 40.4	0.230	56^# / 54^#	0.058
Stage (Durie-Salmon), n	II/III	38/84	28.5 / 54.3	0.257	87.1 / 99.1	0.229
Stage (Durie-Salmon), n	A/B	91/31	40.4 / 65.0	0.277	55^# / 51^#	0.301
IPI, n	I	39	69.3		99.1
	II	34	40.4		70^#
	III	50	52.7	0.764	88.2	0.026
ECOG, n	< 1 / >1	109/12	47.1 / 28.5	0.959	53^# / 31.4	0.301
LDH (IU/L), n	<480 / >480	116/7	52.7 / 17	0.086	53^# / 17	0.001
CRP (mg/L), n	<5 / > 5	51/71	54.3 / 52.7	0.686	85^# /99.1	0.057
PER3	4R/4R	70	40.4		74^#
	4R/5R	64	69.3		57^#
	5R/5R	16	86^#	0.046	100^#	0.349
PER-3	4R/4R	70	40.4		63^#
PER-3	4R/5R -5R/5R	80	89.6	0.028	99.1	0.738

* : median months,

# :10-yrs %

MM: Multiple myeloma, IPI:International Prognostic Index, ECOG:Eastern Cooperative Oncology Group, CRP:C-reactive protein, LDH: Lactate dehydrogenase, OS: Overall survival, PFS: Progression free survival, PER3: Circadian Clock Protein PERIOD 3

Table 4.

Multivariate analysis of 150 MM patients (Cox proportional hazard model backward)

	PFS
		Exp (B)	%95 CI	p
PER-3	4R/4R	0.488	0.284-0.837	0.009
LDH	≥480	0.441	0.170-1.141	0.091
Gender	Female/Male	0.604	0.357-1.022	0.060

[i] MM: Multiple myeloma, PER3: Circadian Clock Protein PERIOD 3, LDH: Lactate dehydrogenase

Progression free survival curves: 4R/4R and 4R/5R-5R/5R

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DOI: https://doi.org/10.2478/bjmg-2022-0026 | Journal eISSN: 2199-5761 (formerly 1311-0160) | Journal ISSN: 1311-0160

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Language: English

Page range: 37 - 43

Published on: May 2, 2023

Published by: Macedonian Academy of Sciences and Arts

In partnership with: Paradigm Publishing Services

Keywords:

PER3,

Related subjects:

Basic medical science,

Basic medical science, other

© 2023 I. Serin, S. Pehlivan, I. Demir, Y. Oyacı, M. Pehlivan, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Volume 25 (2022): Issue 2 (December 2022)

A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism

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Table 3.

Table 4.

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