Inequalities in diagnosis and registration of pediatric very rare tumors: a European study on pleuropulmonary blastoma.

Very rare tumors (VRTs) account for up to 11% of childhood cancers. Dedicated national groups and registries only exist in some European countries. Pleuropulmonary blastoma (PPB) is a very rare intrathoracic pediatric tumor with a potentially severe prognosis. Due to its rarity, it sometimes goes unrecognized. We investigated PPB diagnostic capability and possible correlations between diagnostic performance and VRT-dedicated activities. The number of cases of PPB registered between 2000 and 2014 at pediatric oncology centers in Europe was compared with the number of expected cases. Data sources included VRT registries, population-based cancer registries, and hospital registries. Data were obtained for 25 countries, grouped into 4 geographical regions. The expected cases were 111, and the observed cases were 129. The observed-to-expected ratio was 1.86 for Northern Europe, 1.33 for Southern Europe, 1.22 for Central Europe, and 0.65 for Eastern Europe. More cases than expected were registered in all countries with an official VRT registry.Conclusion: The number of cases observed is consistent with expectations, but disparities exist across Europe. Difficulties in diagnosing PPB emerged in most Eastern countries. The incidence rate of PPB may be underestimated. The creation of VRT-dedicated groups and a European Registry for VRTs could help to reduce inequalities.What is Known:• Very rare pediatric tumors are often not recognized, despite representing almost 11% of childhood cancers .• Pleuropulmonary blastoma is a rare pediatric tumor with a poor prognosis.What is New:• The ability to diagnose and register pleuropulmonary blastoma varies in Europe.Registries dedicated to very rare pediatric tumors improve the diagnostic rates.• The incidence rate of pleuropulmonary blastoma may currently be underestimated.

Genetic characterization of the historical Albanian ethnic minority of Calabria (southern Italy).

Three historical ethnic minorities are present in Calabria: Albanians, Greeks, and Occitans. The Albanian ethnic minority is the more populous, having settled in Calabria between the 15th and 17th centuries, and these populations are now located in the provinces of Cosenza and Catanzaro. In the present study the Albanian population structure is analyzed based on the allele frequencies of six classic genetic markers: ACP, GC, PGM1, AK, ADA, and 6PGD. The results show a significant heterogeneity between the Albanian population in Calabria and the population in Molise. Therefore the cultural and reproductive isolation of the Albanian ethnic minority of Calabria is related to a great genetic peculiarity. Moreover, the frequencies of some alleles, particularly those of the PGM*1W31 variant, and the analysis of the R matrix still show the actual peculiar genetic structure of the Albanians of Calabria, although the genetic flow is evident in the decrease of endogamy and in the increase in the degree of mixing.

Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance.

The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.

Identification of glucose 6-phosphate dehydrogenase deficiency in a population with a high frequency of thalassemia.

High frequencies of both thalassemia trait (5.2%) and glucose 6-phosphate dehydrogenase (G6PD) deficiency for only males (1.3%) have been observed in the Calabrian population. The G6PD activity measurement was carried out on 1239 samples of whole blood from Calabrian subjects of both sexes (age range 10-55) by a differential pH-metry technique which was quite suitable to determine the G6PD deficiency in mass screenings. The analyzed subjects showed: only the thalassemia trait; or only the G6PD deficiency; or only the total iron serum deficiency; or G6PD deficiency associated with the thalassemia trait or with the total iron serum deficiency. The G6PD heterozygous subjects have an enzymatic activity which is masked by both the thalassemia trait and the total iron serum deficiency. In a population showing high frequencies of both thalassemia trait and G6PD deficiency, the comparison of G6PD activity of heterozygous subjects also affected with the thalassemia trait is more reliable if referred to the enzymatic activity of the carriers of the latter inherited anomaly rather than to G6PD activity of normal subjects.

Color-blindness in Calabria (Southern Italy): A north-south decreasing trend.

The frequency of color-blindness (CB) in 13,072 males from 409 towns in Calabria is 5.42%. Regional variation in CB within the three provinces of Calabria was studied: Cosenza (northern), Catanzaro (central), and Reggio Calabria (southern). There is a decreasing trend of mean frequencies of CB from Cosenza to Reggio Calabria through Catanzaro: 6.23%, 4.65%, and 3.43%, respectively. The mean frequencies do not take into account the two ethnic minorities present in Calabria: Albanians and Grecanicans. The frequency of CB mean Albanians (7.40%) and the indigenous Calabrian population (5.25%) differs significantly. Moreover, the Albanians do not show the protoanomalous phenotype. The small sample size of Grecanicans does not permit an evaluation of mean CB frequency. Thus, from the perspective of CB, the Calabria region may be considered a mixture of "genetic isolates" reflecting its historical, sociocultural, demographic, and genetic features. Am. J. Hum. Biol. 12:17-24, 2000. Copyright 2000 Wiley-Liss, Inc.

Endogamy and inbreeding since the 17th century in past malarial communities in the Province of Cosenza (Calabria, Southern, Italy).

Many authors stressed the importance of considering mating patterns, migration and consanguinity when analysing micro-geographic differences in the distribution of the frequency of genetic traits (thalassaemia and glucose 6 phosphate dehydrogenase deficiency (G6PD) in populations living in areas of past malarial endemy. Therefore, the present work was aimed at estimating the reproductive isolation of Calabria, an Italian region that experienced endemic malaria until very recently. The research was carried out on 15311 records of marriage from Parish Books of four villages located in the past malarial area, and four situated in the non-malarial region. Endogamy rates were high in every village and decreased only in the present century as a consequence of the breakdown of isolation. In the earlier periods, the rates ranged between 93-84% in non-malarial villages, and between 96-66% in the past malarial area. The rate of consanguineous marriages was low in all villages: in the malarial area it was 2.15% on average, whereas in the non-malarial villages it ranged between 2-16%. Its trend increased with time almost everywhere. Concerning values, differences between past malarial and non-malarial villages in earlier periods are not consistent as they ranged from 0.1 x 10(-3) to 1 x 10(-3). In the present century, however, a was higher in the non-malarial villages. Observed changes of the coefficient a since the 19th century are due to the increased frequency of first cousin marriages. Isonymy rates were lower than 2% in all past malarial towns in all periods, whereas in nonmalarial villages they ranged between 1.2-9.5% and increased with time. Inbreeding coefficients F are always higher than alpha values, but show the same trend with time. They were between 0.0006-0.0045 in past malarial towns, and between 0.0017-0.024 in non-malarial villages. In non-malarial villages Fn displayed noticeable negative values in two situations in the earlier periods. In conclusion, given the above mating patterns and the observed distribution of frequencies of G6PD deficient hemizygous and thalassemic heterozygous in the investigated villages, there is clear evidence in this area for the absence of any specific role of reproductive isolation and consanguinity on the distribution of genetic traits related to past malaria presence.

Past malaria, thalassemia and woman fertility in southern Italy.

The role of natural selection in maintaining the thalassemia polymorphism is examined in a southern Italy district, in the past affected by malaria endemia. The Haldane's hypothesis that the thalassemia heterozygotes enjoy more protection than the normal homozygotes against the risk of malaria infection, seems to be confirmed by this indirect study at population level. The higher number of children born of the women who lived in the highly endemic villages, where the highest proportion of heterozygotes occurs, supports the hypothesis that the woman fertility contributes to the thalassemia maintenance. The joint effects of the acquired and inherited immunities and of the reproductive compensation are assumed as the mechanisms through which malaria and thalassemia influence fertility.