Childhood leukemia in metropolitan regions in the United States: a possible relation to population density?

Following recent research in Great Britain, the geographic incidence of leukemia and non-Hodgkin's lymphoma among White children in three metropolitan regions of the United States (San Francisco-Oakland, CA; Detroit, MI; and Atlanta, GA) during 1978–82 has been analyzed using census tract-specific data. There was no evidence of a general tendency for cases to cluster geographically, in contrast to results from Britain. Further, rates did not vary with median income or education levls for census tracts. However, there was a statistically significant increasing trend in incidence rates with increasing population density: relative risk for highest relative to lowest category=1.4 (95% percent confidence interval [CI]=1.1–2.0) for White population density, and 1.4 (CI=1.0–2.0) for total population density. The interpretation of these findings is unclear and further investigation is required. It is possible that population density is acting as a surrogate for some virus-related factor.The analyses were performed while be was a Guest Researcher at the Radiation Epidemiology Branch of the US National Cancer Institute. This work was supported partially by the European Commission under contract number FI3P-CT920064f.     

Childhood leukaemia and population movements in France, 1990-2003

In a national study, we investigated the incidence of childhood leukaemia (CL) over a 14-year period in France in relation to several measures based on the proportion of individuals who changed address between the last two national censuses. A positive association was found with the proportion of migrants who came from a distant place. The further the migrants came, the higher was the incidence of leukaemia, particularly among children aged 0-4 years in 'isolated' communes at the time of diagnosis (RR=1.4, 95% CI: 1.1,1.8 in the highest category of migration distance). Although the role of the population density was less obvious, a more marked association was found above a certain threshold. No association with the proportion of commuters was observed.     

Childhood leukaemia, nuclear sites, and population mixing

The excess of childhood leukaemia (CL) in Seascale, near the Sellafield nuclear reprocessing site in rural NW England, suggested that an epidemic of an underlying infection, to which CL is a rare response, is promoted by marked population mixing (PM) in rural areas, in which the prevalence of susceptibles is higher than average. This hypothesis has been confirmed by 12 studies in non-radiation situations. Of the five established CL excesses near nuclear sites, four are associated with significant PM; in the fifth, the Krummel power station in Germany, the subject has not been thoroughly investigated.     

An ecologic study of childhood leukemia and population mixing in Ontario, Canada

Objective: To examine the association between population mixing and the incidence of childhood leukemia, specifically the acute lymphocytic leukemia (ALL) subtype among young children. Methods: This ecologic study was based on incidence rates of leukemia in children aged 0–14 years. The Ontario Cancer Registry was used to identify the residence of 1394 leukemia cases between 1978 and 1992. Ecologic units were composed of census subdivisions in a 5-year period. Percent population change, determined from the Census of Canada, was employed as a measure of population mixing. The relationship between population mixing and childhood leukemia was examined separately after stratifying by the level of geographic isolation, defined according to urban–rural status. Analyses were also conducted separately in specific age groups and for the ALL subtype. Results: Population growth in rural areas was associated with an increased incidence of leukemia, particularly for the ALL subtype in children aged 0–4 years (rate ratio = 1.8, 95% confidence interval 1.1–2.8, for a greater than 20% population change relative to no increase in population). In contrast, an elevated risk due to population mixing was not observed in urban areas. Conclusions: Results from this study are consistent with results from similar studies conducted in the United Kingdom, which are suggestive of a role for an infectious agent in the etiology of childhood leukemia, as proposed in the Kinlen hypothesis.     

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data

We evaluated the infectious aetiology hypothesis of childhood leukaemia that rapid population influx into rural areas is associated with increased risk. Using data from the US SEER program, we found that in changes in rural county population sizes from 1980 to 1989 were associated with incidence rates for childhood acute lymphocytic leukaemia (ALL). The observed associations were strongest among children 0-4 years of age, born in the same state as diagnosis, in extremely rural counties, and when counties adjacent to nonrural counties were excluded. Similar analyses for brain and central nervous system (CNS) cancer in children, a disease less linked to this infectious hypothesis, provide evidence against methodologic bias. Similar evaluations for other decades were not meaningful due to limited sample sizes and, perhaps, increased population mobility.     

Childhood leukemia and magnetic fields in Japan: a case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan

Residential power-frequency magnetic fields (MFs) were labeled as a possible human carcinogen by the International Agency for Research on Cancer panel. In response to great public concern, the World Health Organization urged that further epidemiologic studies be conducted in high-exposure areas such as Japan. We conducted a population-based case-control study, which covered areas inhabited by 54% of Japanese children. We analyzed 312 case children (0-15 years old) newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myelocytic leukemia (AML) in 1999-2001 (2.3 years) and 603 controls matched for gender, age and residential area. Weekly mean MF level was determined for the child's bedroom. MF measurements in each set of a case and controls were carried out as closely in time as possible to control for seasonal variation. We evaluated the association using conditional logistic regression models. The odds ratios for children whose bedrooms had MF levels of 0.4 microT or higher compared with the reference category (MF levels below 0.1 microT) was 2.6 (95% CI=0.76-8.6) for AML+ALL and 4.7 (1.15-19.0) for ALL only. Controlling for some possible confounding factors did not alter the results appreciably. Even an analysis in which selection bias was maximized did not fully explain the association. Most of the leukemia cases in the highest exposure category had MF levels far above 0.4 microT. Our results provided additional evidence that high MF exposure was associated with a higher risk of childhood leukemia, particularly of ALL.     

Acute Complications and Survival Analysis of Childhood Acute Lymphoblastic Leukemia: A 15-year Experience

BackgroundWe evaluated the acute complications that occurred during the treatment of childhood acute lymphoblastic leukemia (ALL) and documented the survival rates of children with ALL.Materials and MethodsWe retrospectively evaluated 110 children with a diagnosis of ALL treated with the Children’s Oncology Group protocol from 1999 to 2014. The demographic, clinical, and laboratory data of 110 patients and acute complications of eligible and evaluable 105 patients were recorded.ResultsOf the 110 patients, 65 were male and 45 were female. The mean age at admission was 8.3 ± 5.2 years. Ninety-seven patients (88.2%) had been diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. Of the 110 patients, 40 (36.3%) were in the standard-risk group and 70 (63.7%) were in high-risk group. Of the 110 patients, 105 had been followed up regularly and evaluated for acute complications. Infection was the most common complication (n = 93; 88.5%), followed by gastrointestinal (n = 29; 27.6%), neurologic (n = 28; 26.6%), metabolic/endocrine (n = 16; 15.2%), drug-related hypersensitivity (n = 16; 15.2%), avascular necrosis (n = 13; 12.3%), thrombotic (n = 11; 10.4%), severe psychiatric (n = 2; 1.9%), and various other (n = 12; 11.4%) complications. Of the 110 patients, 98 were assessed in terms of survival analysis. The 5- and 10-year overall survival rates were both 85.9% (standard error [SE], 3.6%). The relapse-free survival rates at 1, 3, and 5 years were 97.9% (SE, 1.5%), 91.3% (SE, 3%), and 86.3% (SE, 3.7%), respectively.ConclusionChildhood ALL, although categorized as curable malignancy owing to the improvements in treatment strategies in recent years, can cause acute complications affecting various systems. Thus, patients should be treated and followed up by multidisciplinary medical teams with high expertise.     

Childhood leukemia and road traffic: A population-based case-control study

To assess the effect of road traffic exhaust on the risk of childhood leukemia, we carried out a population-based case-control study in the Province of Varese, northern Italy, covered by a population-based cancer registry. All 120 incident cases from 1978-97 were included in the study. Four controls per case, matched by age and gender, were sampled from population files. As index of exposure to traffic exhaust we estimated the annual mean concentration of benzene outside the home using a Gaussian diffusion model. This model uses traffic density (vehicles/day) on nearby main roads, distance between roads and residence, and information on vehicle emissions and weather conditions to estimate benzene concentration. Compared to children whose homes was not exposed to road traffic emissions (<0.1 microg/m(3) of benzene as estimated by the model), the risk of childhood leukemia was significantly higher (relative risk [RR] = 3.91; 95% confidence interval [CI] = 1.36-11.27) for heavily exposed children (over 10 microg/m(3) estimated annual average). For the intermediate exposure group (0.1-10 microg/m(3)) the relative risk was 1.51 (95% CI = 0.91-2.51). These data, considered with other available evidence, suggest that motor traffic emissions can be involved in the etiology of childhood leukemia.     

Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes

Hereditary hemochromatosis (HFE) variants correlating with body iron levels have shown associations with cancer risk, including childhood acute lymphoblastic leukemia (ALL). Using a multi-ethnic sample of cases and controls from Houston, TX, we examined two HFE variants (rs1800562 and rs1799945), one transferrin receptor gene (TFRC) variant (rs3817672) and three additional iron regulatory gene (IRG) variants (SLC11A2 rs422982; TMPRSS6 rs855791 and rs733655) for their associations with childhood ALL. Being positive for either of the HFE variants yielded a modestly elevated odds ratio (OR) for childhood ALL risk in males (1.40, 95% CI = 0.83–2.35), which increased to 2.96 (95% CI = 1.29–6.80) in the presence of a particular TFRC genotype for rs3817672 (Pinteraction = 0.04). The TFRC genotype also showed an ethnicity-specific association, with increased risk observed in non-Hispanic Whites (OR = 2.54, 95% CI = 1.05–6.12; Pinteraction with ethnicity = 0.02). The three additional IRG SNPs all showed individual risk associations with childhood ALL in males (OR = 1.52–2.60). A polygenic model based on the number of variant alleles in five IRG SNPs revealed a linear increase in risk among males with the increasing number of variants possessed (OR = 2.0 per incremental change, 95% CI = 1.29–3.12; P = 0.002). Our results replicated previous HFE risk associations with childhood ALL in a US population and demonstrated novel associations for IRG SNPs, thereby strengthening the hypothesis that iron excess mediated by genetic variants contributes to childhood ALL risk.     

Childhood leukaemia and ordnance factories in west Cumbria during the Second World War

Much evidence has accumulated that childhood leukaemia (CL) is a rare response to a common, but unidentified, infection and in particular that situations involving the unusual mixing of urban and rural groups (approximating to, respectively, groups infected with, and susceptible to, the relevant microorganism) can produce localised epidemics with consequent increases of the infrequent leukaemic complication. During the Second World War, explosives production factories were built and operated at Drigg and Sellafield, and a shell filling factory at Bootle, in west Cumbria, England, requiring substantial numbers of construction workers to be brought into this remote and isolated area. Following the design of an earlier study of CL near large (post-war) rural construction sites, mortality from this disease was investigated with the help of the Office of National Statistics, in the area around these Cumbrian factories where local workers largely lived, during the construction period and with particular reference to the overlapping construction and operational phase when the mixing of local and migrant workers would have been greatest. An excess of leukaemia deaths at ages 1-14 was found during the construction period (observed 3; observed/expected (O/E) 2.2, 95% confidence interval (CI): 0.6, 6.0), which was more marked and statistically significant during the overlap with operations (O 3; O/E 4.5, 95% CI: 1.1, 12.2), especially at ages 1-4 (O 2; O/E 7.1, CI: 1.2, 23.6). A previous investigation did not detect this excess because it considered only a small part of west Cumbria that omitted the communities where most of the workforce lived, having incorrectly attributed the post-war expansion of the village of Seascale (situated between Drigg and Sellafield) to the wartime ordnance factories. The present findings are consistent with the results of the earlier study of rural construction projects and with the general evidence that marked rural-urban population mixing increases the risk of CL.     

Paternal occupational contact level and childhood leukaemia in rural Scotland: a case-control study

In a national Scottish study of 809 cases of leukaemia and non-Hodgkins lymphoma diagnosed in 1950-89 among children aged 0-4 years who were born in Scotland, together with 2363 matched population controls, we investigated one aspect of the infective hypothesis. This concerns whether in rural areas (where the prevalence of susceptible individuals is likely to be higher) the risk is greater among the young children of men whose work involves contacts with many different people, particularly children, as noted in certain childhood infections. A positive trend was found in rural areas across 3 levels of increasing paternal occupational contact (as recorded at birth) by each of 2 previously defined classifications; no such effect was found in urban areas. The rural trend was more marked in that part of the study period with greater population mixing, but the difference from the period with less mixing was not itself significant, leaving open whether these rural findings reflect the extreme isolation of much of rural Scotland, or the effects in such areas of a degree of population mixing. In marked contrast, among the 850 cases and 2492 controls aged 5-14, those in rural areas in the higher population mixing period showed a significantly decreasing trend with increasing paternal occupational contact level. This would be consistent with immunity produced either by earlier infection at ages 0-4 years, or directly by low doses of the infective agent that were largely immunizing at these older ages. The findings overall provide further support for infection underlying childhood leukaemia and for the role of adults.     

Malaysian childhood leukemia: A 13 year review at the University hospital,Kuala Lumpur

A study of 168 cases of childhood leukemia in the University Hospital, Kuala Lumpur reveals no significant differences in incidence or other epidemiological features between Malaysian and Caucasian children. The ratio of lymphoid and myeloid leukemia and the peak in leukemia mortality at 3–4 years is similar. The risk of leukemia and lymphoma is higher among family members of children with leukemia. BCG vaccination has not conferred any protection against leukemia. The response to therapy is similar to that of Caucasian children but more of our patients have poor prognostic features due to later presentation. It is likely that the leukemias are remarkably uniform in geographic distribution and what variations are seen may in part at least, reflect differences in case detection and availability of medical care.     

Processed meats and risk of childhood leukemia (California,USA)

The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and organge juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR]=9.5, 95 percent confidence interval [CI]=1.6–57.6 for 12 or more hot dogs per month, trendP=0.01), and fathers' intake of hot dogs (OR=11.0, CI=1.2–98.7 for highest intake category, trendP=0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.This work was supported by contract No. 799-24 from the Electric Power Research Institute and NIOSH Grant No. R010H01413. Cancer incidence data have been collected under Subcontract 050C-8709 with the California Public Health Foundation. The subcontract is supported by the California Department of Health Services as part of its statewide cancer reporting program, mandated by Heatth and Safety Code section 210 and 211.3. The ideas and opinions expressed herein are those of the authors, and no endorsement of the State of California, Department of Health Services or the California Public Health Foundation is intended or should be inferred.     

Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study

Objective As part of a larger case–control study, the authors evaluated risk of childhood leukemia relative to parental self-reported smoking and alcohol consumption. Methods Children 0–14 years of age diagnosed with leukemia between 1990 and 1994 were ascertained through population-based sources at the time of diagnosis. For each participating case, an age, gender, and area-matched control was randomly selected from provincial government health insurance rolls. Risk factor information was obtained through personal interviews with each child’s parents. Conditional logistic regression models were used to examine risk of leukemia associated with parental smoking and drinking. Results Maternal alcohol consumption prior to conception (OR = 1.37, 95% CI, 0.99–1.90) and during pregnancy (OR = 1.39, 95% CI, 1.01–1.93) was associated with an excess risk of childhood leukemia, with a positive dose-response trend for increasing weekly consumption (p < 0.05). Similar results were observed for children diagnosed with acute lymphoblastic leukemia (ALL). Odds ratios for maternal cigarette smoking before and during pregnancy were consistently elevated above one, but not statistically significant. No relationship was observed with paternal drinking or smoking in the perinatal period. Conclusions Our study suggests that maternal alcohol drinking before or during pregnancy may contribute to an increased risk of childhood leukemia.     

Childhood leukemias and other hematopoietic malignancies: Interdependence between an infectious event and chromosomal modifications

A large number of epidemiological observations suggest an infectious origin of hematopoietic malignancies, including various forms of leukemia, nonHodgkin's lymphomas, Hodgkin's lymphomas and multiple myelomas. Incidence of nonHodgkin's lymphomas and Hodgkin's lymphomas, although not of leukemias, is substantially increased under immunosuppression. Specific chromosomal modifications (translocations) resulting in fusion genes frequently emerge as early, but not sufficient, events for malignant progression in most of these conditions. Presently less than 10% of the global incidence of leukemias and lymphomas can be linked to infections (Epstein‐Barr virus, human T‐lymphotropic retrovirus, human herpesvirus type 8 and Helicobacter pylori). For individual tumor types of the remaining more than 90%, several risk factors have been identified. They include occupational hazards, such as engagement in community services and agriculture, as well as time–space clustering. In childhood leukemias, a protective effect was noted for multiple infections during the first year of life and for at least 6 months of breastfeeding. A high socioeconomic state and absence of multiple contacts during the early phase of life have been described as risk factors. A hypothesis is presented here which combines these observations. It postulates a wide‐spread viral infection, nontumorigenic when replication competent, but potentially leukemiogenic or carcinogenic when replication‐incompetent viral genomes infect cells with specific chromosomal modifications. Existing data on polyoma‐like virus types seem to render members of this or structurally related virus families as putative candidates for these malignancies. © 2009 UICC     

外周血Th17及T淋巴细胞亚群指标与小儿白血病的关系研究

目的 研究与分析外周血Th17及T淋巴细胞亚群指标与小儿白血病的关系.方法 选取60例白血病患儿为观察组,60例健康儿童为对照组,然后检测并比较两组的外周血Th17及T淋巴细胞亚群指标水平,同时将观察组中不同分期与类型白血病患儿的外周血Th17及T淋巴细胞亚群指标水平进行比较,并以Logistic分析上述外周血Th17及T淋巴细胞亚群指标与小儿白血病的关系.结果 观察组的外周血IL-6及CD8+水平高于对照组,其他外周血Th17及T淋巴细胞亚群指标水平则均低于对照组,且不同分期与不同类型白血病患儿其表达水平也存在显著性差异,以Lo-gistic分析显示,外周血Th17及T淋巴细胞亚群指标水平均与小儿白血病有密切的关系.结论 外周血Th17及T淋巴细胞亚群指标在白血病患儿中呈现异常表达的状态,且与本病有密切的关系,可作为疾病的重要监测指标.     

Seasonal variations in the onset of childhood leukemia/lymphoma: April 1996 to March 2000, Shiraz,Iran

Infection has long been suspected as a possible factor in the aetiology of leukemia and lymphoma, one of the most common malignancies in children. Since most viral infections have seasonal variations of onset, if seasonal trends in 1 month of diagnosis of leukemia and lymphoma could be proved, this would be supportive evidence for an infectious aetiology. A total of 367 cases in the Hospitals of Shiraz University of Medical Sciences, from April 1996 through March 2000, who were diagnosed as having acute lymphocytic leukemia (ALL), acute myeloblastic leukemia (AML), Burkitt's lymphoma (BL) chronic myeloblastic lymphoma (CML), Hodgkin's disease (HD) or non-Burkitt's type non-Hodgkin's lymphoma (NBNHL) were analysed. The month of appearance of the first symptom and the date of diagnosis were recorded. ALL demonstrated statistically significant monthly variation in the date of appearance of the first symptom (p < 0.05; peak in October) and the date of diagnosis (p < 0.05; peak in November). Seasonal variation was demonstrated in the date of the first appearance of symptoms in BL (p < 0.042), and in the date of diagnosis in AML (p < 0.049). There was no statistically significant seasonal variation in the month of diagnosis for other groups. Analysis based on the date of the first symptoms and the date of diagnosis for ALL patients, using summer-winter ratios, also showed a significant winter excess (p < 0.001). Our data provide modest support for an autumn-winter peak in the diagnosis of childhood ALL, underlying mechanisms that account for these patterns are likely to be complex and need more definitive studies.