ASSOCIATION OF SELECTED GENE POLYMORPHISMS WITH PROGNOSIS AND TREATMENT RESULTS IN FOLLICULAR LYMPHOMA PATIENTS

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

www.eha.org