Relationship of Epstein-Barr Virus and Interleukin 10 Promoter Polymorphisms with the Risk and Clinical Outcome of Childhood Burkitt Lymphoma

<div><p>Epstein-Barr virus (EBV) is an important environmental factor associated to the development of Burkitt lymphoma (BL) in endemic and intermediate risk regions. However, little is known about the contribution of genetic constitution to the development and clinical response of the disease. The aim of this work was to investigate the role of EBV and Interleukin 10 (<em>IL10</em>) single nucleotide polymorphisms (−1082A/G, −819C/T, −592C/A) and microsatellites (IL10.R and IL10.G) in susceptibility and clinical outcome in pediatric BL patients, in a region with intermediate EBV association frequency. The frequencies of <em>IL10</em> promoter Single nucleotide polymorphisms −1082A/G, −819C/T, −592C/A, and IL10.R and IL10.G microsatellites were compared in 62 pediatric patients and 216 healthy donors. <em>IL10</em> −1082GG and GCC/GCC genotypes were more frequent in patients than in controls, and associated to a higher risk of BL development (GG genotype OR 2.62, 95% CI, 1.25–5.51; <em>P</em> = 0.008; <em>Pc</em> = 0.024). EBV was detected in tumor samples by EBER-ISH in 54.1% of cases. EBV+ patients exhibited a better event free survival (EFS) (<em>P</em> = 0.019) than EBV− patients. Carriers of <em>IL10</em> R3-GCC had worse EFS (<em>P</em> = 0.028). Our results suggest a risk effect and an independent prognostic value of <em>IL10</em> polymorphisms and EBV in childhood BL patients.</p> </div

Genotypic frequencies of SNP-1082G/A in EBV+ and EBV− Burkitt lymphoma cases.

<p>Genotypic frequencies of SNP-1082G/A in EBV+ and EBV− Burkitt lymphoma cases.</p

Comparisons of haplotypes and combinations between BL patients and controls.

1<p>N represent the number of individuals and 2N the number of chromosomes carrying each IL10 proximal haplotype or combination;</p>2<p>P values column: for each category, the first p value (italics) represents the comparison of cases vs. controls, by Chi-square Test; and the following represent the significance of the odds ratio (OR), as calculated by logistic regression, having case vs. control as dependent variable and each IL10 haplotype, combination or family as a covariate.</p

Clinical and demographic characteristics of Burkitt lymphoma patients.

<p>N: number of cases with available data.</p>1<p>St. Jude's staging according to Murphy (ref. 23).</p>2<p>Risk group as classified in the Berlin-Frankfurt-Munster (BFM) 90 protocol, adopted by the Instituto Nacional de Câncer – INCA LNH-98 (Brazil) protocol for the treatment of childhood Non Hodgkin lymphoma (ref. 24).</p

Distributions of Event free survival (EFS) probabilities according to (A) EBV status; (B) presence of IL10.01 family; (C) presence of IL10.G12 microsatellite allele at RG3; ■ positive; • negative; (D) IL10/EBV combination of risks; ▲EBV−/IL10.01−; ✱EBV+/IL10.01+; EBV−/IL10.01+; ♦ EBV+/IL10.01−.

<p>Distributions of Event free survival (EFS) probabilities according to (A) EBV status; (B) presence of IL10.01 family; (C) presence of IL10.G12 microsatellite allele at RG3; ■ positive; • negative; (D) IL10/EBV combination of risks; ▲EBV−/IL10.01−; ✱EBV+/IL10.01+; EBV−/IL10.01+; ♦ EBV+/IL10.01−.</p