Affiliations: [a] Tecnológico de Monterrey, Escuela Nacional de Medicina, Monterrey, Nuevo León, México | [b] Servicio de Hematología, Unidad Médica de Alta Especialidad IMSS No.25, Monterrey, Nuevo León, México | [c] Tecnológico de Monterrey, Centro de Agrobiotecnología, Monterrey, Nuevo León, México
Correspondence:
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Corresponding author: Sean-Patrick Scott, Av. Morones Prieto #3000 Poniente, Edificio CITES, Colonia Los Doctores, C.P. 64710 Monterrey, Nuevo León, México. Tel.: +52 81 8888 2161; Fax: +52 81 8888 2019; E-mail:[email protected]
Abstract:
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most
common subtype of malignant lymphoma. Presently, one of the most important
clinical predictors of survival in DLBCL patients is the International
Prognostic Index (IPI). Circadian rhythms are the approximate 24 hour
biological rhythms with more than 10 genes making up the molecular clock. OBJECTIVE: Determine if functional single nucleotide polymorphism
in circadian genes may contribute to survival status in patients diagnosed
with diffuse large B-cell lymphoma. METHODS: Sixteen high-risk non-synonymous polymorphisms in
circadian genes (CLOCK, CRY2, CSNK1E, CSNK2A1, NPAS2, PER1, PER2, PER3,
PPP2CA, and TIM) were genotyped by screening PCR. Results were visualized by
agarose gel electrophoresis and confirmed by two-direction sequencing.
Clinical variables were compared between mutated and non-mutated groups.
LogRank survival analysis and Kaplan-Meier method were used to calculate the
overall survival. RESULTS: PER3 rs10462020 variant showed significant difference in
overall survival between patients containing mutated genotypes and those
with non-mutated genotypes (p = 0.047). LDH levels (p = 0.021) and IPI score
(p < 0.001) also showed differences in overall survival. No clinical
differences were observed in mutated vs. non-mutated patients. CONCLUSIONS: This work suggests a role of PER3 rs10462020 in
predicting a prognosis in DLBCL overall survival of patients.
Keywords: Circadian rhythm, single nucleotide polymorphism, diffuse large B-cell lymphoma, PER3, survival, biomarker
