Childhood leukemia in the vicinity of Canadian nuclear facilities

An ecologic study was conducted to determine whether leukemia rates among children born to mothers residing in the vicinity of Ontario (Canada) nuclear facilities differed from the provincial average. Childhood leukemia mortality and incidence ratios for the period 1950 to 1987 were examined for five regions within 25 km of a nuclear facility. The nuclear facilities included a research development facility, a uranium refinery, a uranium mining and milling facility, and two nuclear-power generating stations. Overall, the observed number of leukemia deaths (O=54) was slightly greater than expected (E=46.1) during the period when the facilities operated, but the difference was not statistically significant (O/E=1.17,95 percent confidence interval [CI]=0.88–1.53). There was no indication of a birth cohort effect, as the mortality ratios based on place of birth were not significantly greater than the mortality ratios based on place of death. In the analyses of individual facilities, CIs included the null value and were generally wide because of the small observed and expected numbers; however, in the vicinity of the nuclear generating stations, the observed relative excess of leukemia deaths (O=36, O/E=1.40) had a lower confidence limit that was close to the null value.Drs McLaughlin, Clarke, and Nishri are with the Ontario Cancer Treatment and Research Foundation, Toronto, Ontario, Canada; Drs McLaughlin and Clarke are affiliated also with the University of Toronto, Dr Anderson is with the University of British Columbia, Vancouver, Canada. Address correspondence to Dr McLaughlin, Ontario Cancer Treatment and Research Foundation, 7 Overlea Boulevard, Toronto, Ontario, Canada M4H-1A8. This research project was conducted in the Division of Epidemiology and Statistics of the Ontario Cancer Treatment and Research Foundation. Financial support was received from the Atomic Energy Control Board of Canada.     

Childhood leukemia following phototherapy for neonatal hyperbilirubinemia (Denmark)

To test the hypothesis that exposure to high intensity lightning (around 400 nanometers) in neonatal nurseries increases the incidence of childhood leukemia, over 55,120 newborn children treated with phototherapy for hyperbilirubinemia were identified from the Danish Hospital Discharge Register for 1977–89. Linkage of the roster with the national cancer registry through 1991 revealed 87 childhood cancers, whereas 85 were expected from the rates for the general population. The incidence of leukemia in 34 children was not unusual (standardized incidence ratio [SIR]=1.2, 95 percent confidence interval [CI]=0.8–1.7). Subgroup analyses revealed no remarkable patterns for any category of leukemia subtype, gender, or age at diagnosis. We conclude that whole-body exposure to phototherapy (420–470 nm) shortly after birth is not a significant risk factor for childhood leukemia.     

Aggregation of childhood leukemia in geographic areas of Greece)

A total of 872 children aged up to 14 years, who were diagnosed withleukemia in Greece during the decade 1980-89, were allocated by place ofresidence to the 601 administrative districts of the country. Evaluation ofspatial clustering was done using the Potthoff-Whittinghill method, whichvalidly assesses heterogeneity of leukemia risk among districts with variableexpected numbers of cases. There was highly significant evidence for spatialclustering occurring particularly among children living in urban and, to alesser extent, semi-urban areas. The evidence was stronger for childrenyounger than 10 years old, applied also to children in different five-yearage groups, and persisted when cases of acute lymphoblastic leukemia wereanalyzed separately. These findings provide support to the hypothesis thatlocalized environmental exposures could contribute to the etiology ofchildhood leukemia, but they cannot distinguish between exposures of physicalor chemical nature, nor can they exclude socially conditioned patterns ofexposure to infectious agents.     

Incidence of childhood leukaemia in the vicinity of nuclear sites in France, 1990-1998

Overall, 670 cases (O) of childhood leukaemia were diagnosed within 20 km of the 29 French nuclear installations between 1990 and 1998 compared to an expected number (E) of 729.09 cases (O/E=0.92, 95% confidence interval (CI)=[0.85-0.99]). Each of the four areas defined around the sites showed non significant deficits of cases (0-5 km: O=65, O/E=0.87, CI=[0.67-1.10]; 5-10 km: O=165, O/E=0.95, CI=[0.81-1.10]; 10-15 km: O=220, O/E=0.88, CI=[0.77-1.00]; 15-20 km: O=220, O/E=0.96, CI=[0.84-1.10]). There was no evidence of a trend in standardised incidence ratio with distance from the sites for all children or for any of the three age groups studied. Similar results were obtained when the start-up year of the electricity-generating nuclear sites and their electric nuclear power were taken into account. No evidence was found of a generally increased risk of childhood leukaemia around the 29 French nuclear sites under study during 1990-1998.     

An examination of the sensitivity of reported trends in childhood leukemia incidence rates to geographic location and diagnostic coding (United States)

Background: There have been conflicting reports of increased incidence of childhood leukemia in the United States with some, but not other, registries reporting increasing rates over the past two decades. Because of the reported discrepancy in childhood leukemia incidence rates an analysis of the SEER database was undertaken. Methods: The latest SEER data (1973–1995) were analyzed for trends in childhood (age 0–14) leukemia incidence rates by histologic group (all leukemia combined, acute lymphocytic leukemia (ALL), acute mylogenous leukemia (AML), and other acute leukemia) for each SEER reporting region. Results: A significant increase in ALL during 1973–1995 was observed in the combined SEER data, but the increase was a function of whether the first 3 years, data from the SEER Detroit reporting region are included. For the years 1973–1975 the Detroit region reported to much lower rates for ALL and much higher rates for other acute leukemias relative to the other SEER regions, resulting in an exaggerated temporal increase in ALL. Conclusion: Excluding both the temporal variability, and coding differences for Detroit in the 1973–1975 time frame, there has been no significant increase in childhood leukemia of any histologic group or age category in the United States from the 1970s to 1990s.     

抗原处理相关转运因子在小儿急性白血病患者中的表达及其临床意义

背景与目的:抗原处理相关转运因子(transporterassociatedwithantigenprocessing,TAP)参与免疫监视,因而可能与肿瘤发生有关。本文旨在探讨急性白血病TAP分子表达及其临床意义,探讨急性白血病的治疗策略。方法:采用RT-PCR检测34例初治急性淋巴细胞白血病(acutelymphoblasticleukemia,ALL)(初治组)、15例复发ALL(复发组)及20例急性髓系白血病(acutemyeloidleukemia,AML)患者骨髓中TAP亚单位TAP1和TAP2的表达。20例无全身性疾病外科住院患儿作为对照组。使用数码成像分析仪测定并计算扩增条带的相对于阳性内对照GAPDH的吸光度(A)值。结果:ALL初治组和ALL复发组的TAP1A值(分别为0.448±0.167和0.169±0.021)及TAP2的A值(分别为0.196±0.180和0.112±0.020)均低于对照组,P均<0.01;AML组TAP2的A值低于对照组(P<0.01);ALL复发组TAP1的A值低于ALL初治组,P<0.05;ALL初治组复发者(6/34)TAP1的A值(0.215±0.159)较持续完全缓解(constantcompleteremission,CCR)者低(24/34,0.462±0.189,P<0.05)。结论:小儿ALL和AML均存在TAP分子低表达,这可能促使白血病细胞逃避免疫监视;TAP1亚单位低表达可能与ALL的复发有关。     

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.     

田湾核电站周围居民2001～2004年恶性肿瘤发病分析

[目的]分析田湾核电站运行前30km范围内居民恶性肿瘤发病情况，为评估核电站辐射对人群的影响提供科学依据。[方法]登记报告田湾核电站30km范同内的常住人口恶性肿瘤病例，并补充开展恶性肿瘤回顾性调查。计算发病率、标化发病率、累积发病率、标化截缩率等指标。[结果]恶性肿瘤发病率为155．78／10万，标化发病率为133．27／10万，男性所患恶性肿瘤前5位是肺癌、胃癌、食管癌、肝癌和膀胱癌；女性前5位是乳腺癌、肺癌、胃癌、卵巢癌、食管癌。白血病、甲状腺恶性肿瘤、乳腺癌等与核辐射相关疾病发病率依次为6．63／10万、3．11／10万，33．49／10万。[结论]核电站运行前该地区恶性肿瘤以肺癌和消化道恶性肿瘤为主，白血病、甲状腺恶性肿瘤、乳腺癌发病率高于2004年江苏省内监测点数据，需在该地区持续开展恶性肿瘤监测，以评估核电站对恶性肿瘤的影响。     

Increasing incidence of childhood leukemia in Northwest Italy, 1975-98

Although some childhood cancer registries reported increasing incidence, the evidence and magnitude of time trends in the incidence of childhood leukemia are debated and the scientific evidence is conflicting. Only limited data have so far been supplied from Southern European countries. We present an analysis of the incidence trend of childhood leukemia in Piedmont (NW Italy) in 1975-98, based on data from the population-based childhood cancer registry. The Childhood Cancer Registry of Piedmont has been recording cases of childhood neoplasms since 1967. Procedures have been uniform and are based on an active search for cases and relevant information. Only cases with confirmed residence in Piedmont at diagnosis are included. Eight hundred cases of leukemia (622 acute lymphoblastic [ALL], 133 acute nonlymphoblastic [AnLL], 45 other and unspecified) were recorded in the period 1975-98 considered in our study. Incidence trends were analyzed using piecewise regression and Poisson regression, based on annual incidence rates. As results from the 2 analyses were similar, only the former were reported. In the age group 1-4 years, a statistically significant annual 2.6% increase in incidence rate of ALL (adjusted by age and gender; 95% confidence interval [CI] 1.13-4.13) was estimated. There was no evidence of increase in other age groups. During 1980-98, a statistically significant 4.4% annual increase (95% CI 1.86-6.90) was seen for pre-B-All in the age group 1-4 years. An increase was also seen for T-ALL that was not statistically significant. Sensitivity analyses were conducted, with no relevant differences from the main results. Our data suggest an increasing trend in ALL incidence for children between the ages of 1 and 4 years. These results are unlikely to be explained by changes in quality of data or exhaustiveness in reporting in the study period. The results were not changed in the sensitivity analyses we conducted. Possible causes to be investigated include environmental factors, changes in family size and parental age, socioeconomic conditions and geographical distribution of cases.     

儿童急性淋巴细胞白血病在德国的治疗--COALL-92方案521例临床及疗效分析

目的：总结分析德国应用ＣＯＡＬＬ－９２方案（Ｃooperative mrlticenter treatment strdy for childhood with acute lymphoblastic leukemia of the German Pediatric Oncology and Hematology Society ＣＯＡＬＬ－９２－Ｓtudy/ＧＰＯＨ）治疗儿童急性淋巴细胞白血病的临床疗效。方法：１９９２～１９９７年间在德国１９所儿童 肿瘤治疗中心人同合作采用统一的诊断标准及治疗方案（ＣＯＡＬＬ－９２－ＳＴＵＤＹ/ＧＰＯＨ）治     

Family cancer history and risk of childhood acute leukemia (France)

OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.     

Incidence of leukemia in Asian migrants to the United States and their descendants

Objective: To generate clues regarding the causes of leukemia we compared leukemia incidence rates among Asian-American immigrants and their descendants to those of United States-born whites. Methods: 535 Asian and 6629 white residents diagnosed with leukemia were identified through the Surveillance, Epidemiology and End Results Program during 1973 through 1986 in Hawaii, San Francisco/Oakland, and western Washington. A special tabulation of the 1980 US census was used to estimate the size and composition of the population at risk in these three areas. Results: The incidence of leukemia, either considered as a whole or as individual types, did not appreciably vary between US-born and foreign-born Asian Americans. For all forms of leukemia combined the rates per 100,000 person-years among males were 6.5 for foreign-born Chinese, 7.4 for foreign-born Japanese, and 7.5 for foreign-born Filipino as compared to 7.5 for US-born Chinese, 7.1 for US-born Japanese, and 5.4 for US-born Filipino. The rates in foreign-born Asian females and US-born Asian females were also similar. Asian Americans had a lower incidence of leukemia than US whites (rate of 13.3/100,000 person-years), particularly for chronic lymphocytic leukemia. Conclusions: Irrespective of birthplace, Asian Americans possess one or more characteristics which make their risk for leukemia less than that of US whites.     

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.     

Geographic clustering of testicular cancer incidence in the northern part of The Netherlands

Geographic variations in testicular cancer incidence may be caused by differences in environmental factors, genetic factors, or both. In the present study, geographic patterns of age-adjusted testicular cancer incidence rates (IRs) in 12 provinces in The Netherlands in the period 1989-1995 were analysed. In addition, the age-adjusted IR of testicular cancer by degree of urbanization was evaluated. Cancer incidence data were obtained from the Netherlands Cancer Registry. The overall annual age-adjusted IR of testicular cancer in The Netherlands in the period 1989-1995 was 4.4 per 100000 men. The province Groningen in the north of the country showed the highest annual IR with 5.8 per 100000 men, which was higher (P < 0.05) than the overall IR in The Netherlands (incidence rate ratio (IRR) 1.3, 95% confidence interval (CI) 1.1-1.6). The highest IR in Groningen was seen for both seminomas and non-seminomas. In addition, Groningen showed the highest age-specific IRs in all relevant younger age groups (15-29, 30-44 and 45-59 years), illustrating the consistency of data. The province Friesland, also situated in the northern part of the country, showed the second highest IR of testicular cancer with 5.3 cases per 100000 men per year (IRR 1.2, 95% CI 1.0-1.5, not significant). This mainly resulted from the high IR of seminoma in Friesland. Analysis of age-adjusted IRs of testicular cancer by degree of urbanization in The Netherlands showed no urban-rural differences at analysis of all histological types combined, or at separate analyses of seminomas and non-seminomas. Geographic clustering of testicular cancer seems to be present in the rural north of The Netherlands with some stable founder populations, which are likely to share a relatively high frequency of genes from common ancestors including genes possibly related to testicular cancer. Although this finding does not exclude the involvement of shared environmental factors in the aetiology of testicular cancer, it may also lend support to a genetic susceptibility to testicular cancer development. Testicular cancer cases in stable founder populations seem particularly suitable for searching for testicular cancer susceptibility genes because such genes are likely to be more frequent among affected men in such populations.     

Incidence of childhood leukemia before and after shut down of nuclear power plants in Germany in 2011: A population-based register study during 2004 to 2019

The association between leukemia and proximity to nuclear-power-plants (NPPs) has been assessed in several countries with inconsistent results. A case-control study from Germany had shown an increased risk for childhood leukemia (diagnoses 1980-2003) near NPPs. Germany began shutting down nuclear reactors in 2011, following the Fukushima disaster. We tested whether the previously observed association between leukemia and proximity to NPP persisted despite the shutdown. We used an ecological study design to investigate the incidence of leukemia during 2004 to 2019 in children aged 0 to 14 years living near NPPs where at least one reactor was shut down in 2011. We defined study and control areas as municipalities whose surface area was at least 75% within 10 km or between 10 and 50 km of NPPs, respectively. We calculated age-standardized rates and incidence rate ratios (IRR) using control-areas as the reference. We also computed standardized incidence ratios (SIR) separately for each NPP using incidence rates of the German population as a reference. IRR decreased from 1.20 (95% confidence interval: 0.81-1.77) in 2004 to 2011 to 1.12 (0.75-1.68) in 2012 to 2019. Analyses of single plants showed an excess of childhood leukemia during 2004 to 2019 for the Unterweser-NPP, based only on three cases, and the Krümmel-NPP (n = 14; SIR: 1.98, 1.17-3.35). We found slightly decreasing of leukemia incidence rate ratios after the shutdown of nuclear reactors in 2011. Due to the small number of cases, risk estimates have large uncertainty. Further research including a longer follow-up is warranted. The consistent excess of incidence cases around Krümmel may require analytical epidemiological analysis.     

Evaluation of radiation therapy factors in prophylactic central nervous system irradiation for childhood leukemia: A report from the Children's Cancer Study Group

The results of six different types of central nervous system (CNS) prophylaxis were studied in two successive Children's Cancer Study Group clinical trials of children with acute leukemia. Radiation therapy doses and technical factors were analyzed in relation to survival, relapse-free survival, bone marrow and CNS relapse rates, and the toxicities encountered in 656 study children. They were randomized among: (1) 2400 rad to the craniospinal axis (CS) and 1200 rad to the abdomen and gonad (2) 2400 rad CS, (3) 2400 rad to the cranium (Cr) + intrathecal methotrexate (IT/MTX), (4) IT/MTX alone, (5) 1800 rad CS, and (6) 1800 rad Cr + IT/MTX. Hematologic, gastrointestinal and infectious disease complications were highest in group 1. The patients were divided into low and high risk categories, defined as those with initial white blood cell counts below and above 20,000/cumm. for outcome analyses. No statistically significant differences were detected in the five-year rates for relapse-free survival or survival, nor for CNS or bone marrow relapse among the 5 irradiated groups when equipment variables, total doses, field arrangements, fractionation, and protraction were analyzed. These results should be interpreted in the light of the group 4 children who had the highest CNS relapse rates (e.g., 33 % for low risk patients vs. 4–16% for their counterparts in the other 5 groups), but nonetheless had a generally similar bone marrow and survival experience. Exceptions to the foregoing are the better five-year survival rates of 64 and 73 % respectively for group 3 and group 6 high-risk boys, contrasted with 25–42 % for their counterparts in the other 4 groups.