Apostolos Pourtsidis

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets.

Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL

We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol.

Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis.

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta‐analysis included all published cohort (n = 2) and case–control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (‐2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non‐Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional metaregression analysis was conducted to explore dose–response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03–1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95% CI: 0.66–1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95% CI = 0.96–1.27, fixed effects model), possibly because of the case‐mix of NHL to HL. No dose–response association was revealed in the metaregression analysis. In conclusion, this meta‐analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose–response phenomena in the NHL association, however, warrants accumulation of additional data.

Serum Adiponectin As a Predictor of Childhood Non-Hodgkin's Lymphoma: A Nationwide Case-Control Study

PURPOSE To our knowledge, this is the first study exploring the association of childhood non-Hodgkins lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined. PATIENTS AND METHODS We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed. RESULTS Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively. CONCLUSION Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.

Genetic variants in immunoregulatory genes and risk for childhood lymphomas

To investigate whether single nucleotide polymorphisms (SNPs) in key cytokine and innate immunity genes influence risk for childhood lymphomas, we genotyped 37 children with Hodgkin’s (HL) and 48 with non‐Hodgkin’s lymphoma (NHL), aged (1 month–14 yr), along with their 85 age‐ and gender‐matched controls suffering from mild medical conditions. Genotypic analysis was performed for 10 SNPs from nine genes with important role in immunoregulatory pathways (IL4, IL4R, IL6, IL10, IL12, IL18, TNFα, IFNγ, CD14). Analysis of SNPs genotypes revealed that the CD14 −159 C>T polymorphism was associated with significantly increased risk for HL regarding both the CC and CT genotypes (ORCC: 5.36; 95% CI, 1.30–22.14; P = 0.02, ORCT: 3.76; 95% CI, 1.00–14.16; P = 0.05). An indicative association between IL18−137 G>C polymorphism with the CC genotype and NHL did not reach, however, statistical significance (ORCC, 3.78; 95% CI, 0.87–16.38; P = 0.08). In conclusion, our findings suggest that genetic variation in the CD14–159 loci may be associated with childhood HL risk; these preliminary findings need to be further confirmed in sizeable multi‐centre studies along with determination of cytokines, which could provide an insight on the biologic basis underlying these findings.

ELECTRICAL POWER LINES AND CHILDHOOD LEUKEMIA: A STUDY FROM GREECE

Residential proximity to electrical power lines of different voltage in relation to childhood leukemia was investigated through a case-control study undertaken in Greece during 1993-1994. The study comprised 117 incident cases of childhood leukemia and 202 age-, gender- and place-of-residence-matched controls. Four measures of exposure to magnetic fields were developed, using data provided by the Public Power Corporation of Greece: Voltage (V) divided by the distance (d), V/d2, V/d3 and an adaptation of the Wertheimer-Leeper code. Conditional-logistic-regression modeling was used to adjust for potential confounding influences of 18 variables. No significant trends of childhood leukemia risk with increasing exposure levels were noted, nor were there statistically significant elevations of disease risk at the higher exposure levels in each measure of exposure. These results do not support a causal link between residential proximity to electrical high-voltage wires and childhood leukemia risk, but in themselves do not refute a weak empirical association.

Childhood central nervous system tumours: Incidence and time trends in 13 Southern and Eastern European cancer registries

AIM Following completion of the first 5-year nationwide childhood (0-14 years) registration in Greece, central nervous system (CNS) tumour incidence rates are compared with those of 12 registries operating in 10 Southern-Eastern European countries. METHODS All CNS tumours, as defined by the International Classification of Childhood Cancer (ICCC-3) and registered in any period between 1983 and 2014 were collected from the collaborating cancer registries. Data were evaluated using standard International Agency for Research on Cancer (IARC) criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic subgroup were calculated, whereas time trends were assessed through Poisson and Joinpoint regression models. RESULTS 6062 CNS tumours were retrieved with non-malignant CNS tumours recorded in eight registries; therefore, the analyses were performed on 5191 malignant tumours. Proportion of death certificate only cases was low and morphologic verification overall high; yet five registries presented >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant tumours was 23/10(6) children, with the highest rates noted in Croatia and Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although astrocytomas were overall the most common subgroup (30%) followed by embryonal tumours (26%), the latter was the predominant subgroup in six registries. CONCLUSION Childhood cancer registration is expanding in Southern-Eastern Europe. The heterogeneity in registration practices and incidence patterns of CNS tumours necessitates further investigation aiming to provide clues in aetiology and direct investments into surveillance and early tumour detection.

Allergy-associated symptoms in relation to childhood non-Hodgkin's as contrasted to Hodgkin's lymphomas: a case-control study in Greece and meta-analysis.

An increase of the prevalence of childhood allergic diseases and the incidence of childhood Hodgkins (HL) and non-Hodgkins lymphoma (NHL) were reported in the late 20th century. Among adults, several studies point to an inverse association with lymphoma; it remains to be confirmed whether allergy is also related to childhood lymphomas and whether the association, if any, is of an aetiologic nature. Between 1996 and 2008, 277 children (aged 0-14 years) with HL (N = 111) or NHL (N = 166) were enrolled in Nationwide Registry for Childhood Hematological Malignancies (NARECHEM), a Greek hospital-based-registry of childhood hematological malignancies. Hospital controls were individually matched to cases on age and sex. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95%confidence intervals (CIs) for associations of allergic diseases and other covariates with childhood HL or NHL risk. Subsequently, we combined our results with those of a French case-control study in a meta-analysis amounting to a total of 330 NHL cases/1478 controls and 239 HL cases/959 controls. After controlling for sociodemographic, perinatal and environmental factors, childhood NHL was less prevalent among children with allergy-associated symptoms overall (OR:0.50, 95%CI:0.27-0.92) or a history of asthma (OR:0.43, 95%CI:0.21-0.88). By contrast, allergy did not seem to be associated with childhood HL risk, although statistical power was limited. Fewer seaside holidays and higher birth weight were also associated with increased childhood NHL risk. The combined OR of the two studies for the association of asthma with NHL risk was: 0.52, 95%CI:0.32-0.84, whereas for HL: 0.86, 95%CI:0.51-1.45. Allergy seems to be strongly and inversely associated with childhood NHL. It remains to be elucidated in future investigations comprising larger populations, focusing on specific disease subtypes and employing more pertinent study-designs, whether this association is genuinely protective.

Adipocytokines in relation to Hodgkin lymphoma in children.

This case–control study aims to explore the association of serum adiponectin/leptin with childhood Hodgkin lymphoma (HL). Study participants were 75 children with histologically confirmed HL, registered in the Nationwide Registry for Childhood Haematological Malignancies and 75 age‐ and gender‐matched controls. Multiple conditional logistic regression analyses were performed, adjusting for sociodemographic and lifestyle parameters. Adiponectin levels were consistently higher among cases in all models with ORs >1.25; 95% CIs ranging from 0.9 to 1.8 and P‐values from 0.09 to 0.20. By contrast, there was no association of serum leptin with HL. In conclusion, elevated serum adiponectin might be a risk factor for childhood HL. Pediatr Blood Cancer 2010;54:311–315.

Childhood central nervous system tumour mortality and survival in Southern and Eastern Europe (1983-2014 ): Gaps persist across 14 cancer registries.

AIM Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region. METHODS Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan-Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants. RESULTS Variations in mortality (8-16 per million) and survival (5-year: 35-69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (-2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1-1.4). CONCLUSION Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe.