ASSOCIATION OF SELECTED GENE POLYMORPHISMS WITH PROGNOSIS AND TREATMENT RESULTS IN FOLLICULAR LYMPHOMA PATIENTS
Author(s): ,
Elena Tothova
Affiliations:
Dpt of Clinical and Medical Biophysics,LF UPJS,Kosice,Slovakia
,
Adriana Kafkova
Affiliations:
Dpt.of Hematology,HEMKO l.t.d,Kosice,Slovakia
,
Lucia Klimcakova
Affiliations:
Dpt of Medical Biology,LF UPJS,Kosice,Slovakia
,
Juraj Duras
Affiliations:
Dpt of Hematooncology,FNO and OU,Ostrava,Czech Republic
,
Jan Salagovic
Affiliations:
Dpt of Medical Biology,LF UPJS,Kosice,Slovakia
Roman Hajek
Affiliations:
Dpt of Hematooncology,FNO and LF OU,Ostrava,Czech Republic
EHA Learning Center. Tothova E. Jun 12, 2015; 102905
Disclosure(s): University UPJS, Kosice, Slovakia
Dpt of Clinical and Medical Biophysics
Prof. Dr. Elena Tothova
Prof. Dr. Elena Tothova

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Abstract: PB1944

Type: Publication Only

Background
Biological studies suggest that a host immunologic environment
plays a major role in follicular lymphomagenesis, which is partly
determined by host genetic background. Cytokines are key regulators of
immune function and regulation, they are highly polymorphic, and have been
implicated in lymphoma etiology and prognosis. To date, few studies
addressing  the association of polymorphisms with prognostic indicators and
results of the treatment in follicular lymphoma have been carried out.

Aims
We analyzed the effect of polymorphisms of selected genes on
some indicators of prognosis, response to treatment regimen and survival
rate.



Methods
We genotyped 4 single nucleotide polymorphisms (SNPs) from 44
candidates' cytokine and immune genes in 64 follicular lymphoma patients
who had participated in our study. Baseline clinical data and survival
rates were obtained from cancer registry files. Genotyping of polymorphisms
(IL2 rs 2069762, IL12B rs 3212227, FCGR2A rs 1801274, C1QA rs172378) was
performed by the method of analysis of melting curve according to real time
PCR by using Eco Real-Time PCR system. Statistical analysis was executed by
using statistical software SPSS with the use of following tests:
chi-kvadrat test, Fisher exact test, Kaplan-Meier analysis  and Cox regres model. P=0.05 was considered as level of statistical significance. Following genetic models were tested:
codominant, recessional and dominant.



Results
The median age at diagnosis was 53 years (range, 23–76), 41% men,
37% of patients were in high risk, 8 (12.5%) patients died during the
follow-up, with a median follow-up of 59 months (range, 29 – 79 months) for
surviving patients.  The dominant genetic model, IL12B allele carriers rs 3212227G
had achieved in comparison to TT homozygotes significantly more complete
remissions after first-line treatment ( 95.5% vs 67.6%, p= 0.018, Fisher exact
test). Other 3 polymorphisms were not associated with 1.line treatment
(R-CVP, R-CHOP). Statistical significance limit was observed for the association
with mortality rate for the recessional genetic model, while the carrier
homozygotes CC polymorphism rs 2069762 IL2 showed a pattern of higher
mortality rate, compared to carriers of allele A (40% vs. 12%, p = 0.144). In
the Kaplan-Meier survival analysis, we observed significantly shorter time for
overall survival ( OS) in the group CC homozygotes compared to carriers
allele polymorphism IL2rs2069762 (34 vs 166 months; p<0.001); this
difference between genotypes remained statistically significant after adjustment to age and sex in the Cox regression model (P=0005).

Summary
In summary, the results of the project have shown an
association of several polymorphisms to response to treatment, mortality
and survival rates. For the most important prognostic consider
polymorphism IL12B rs3212227, where the G allele was associated with higher frequency of achieving complete remission in the group followed. Given the small number of patients in the
study, for the final analysis and possible use of the results in practice
it is necessary to evaluate larger population of patients with follicular
lymphoma.

Keyword(s): Follicular lymphoma, Polymorphism, Survival, Treatment

Session topic: Publication Only
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