Stillbirths and male irradiation.
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Abnormalities, Radiation-Induced↗
Biomedical subjects
L L Robison
Publications and source records attributed to L L Robison.
Do confounding or selection factors of residential wiring codes and magnetic fields distort findings of electromagnetic fields studies?
In contrast with several previous studies, our recent large case-control study found little association between childhood acute lymphoblastic leukemia (ALL) and electric-power-line wire codes. Here we examine internal evidence from our study to assess the possibility that selection bias and/or confounding may have affected the findings. We compared the relation between childhood ALL and wire codes and direct measurements of magnetic fields in subjects who participated in all phases of the study with the relation in all subjects, including those who declined to allow access inside the home. We found that the odds ratio for ALL among those living in homes with very high current configurations increased by 23% when 107 "partial participants" were excluded. We found similar, but slightly smaller, increases in the odds ratios when we performed the same comparisons using direct measurements of magnetic fields, excluding subjects who allowed only a measurement outside the front door. "Partial participants" tended to be characterized by lower socioeconomic status than subjects who participated fully, suggesting possible selection bias. We also examined the relation between a large number of potential confounding variables and both proxy and direct measurements of magnetic fields. Univariate adjustment for individual variables changed the odds ratio for ALL by less than 8%, while simultaneous adjustment for several factors reduced the estimate by a maximum of 15%. We conclude that while confounding alone is unlikely to be an important source of bias in our own and previous studies of magnetic fields, selection bias may be more of a concern, particularly in light of the generally low response rates among controls in case-control studies.
Case-Control Studies↗
Glutathione S-transferase polymorphisms in children with myeloid leukemia: a Children's Cancer Group study.
GSTM1 and GSTT1 are polymorphic genes. Absence of enzyme activity is due to homozygous inherited deletion of the gene, reducing detoxification of carcinogens such as epoxides and alkylating agents and potentially increasing cancer risk. We hypothesized that GST null genotype would increase risk of acute myeloid leukemia and myelodysplasia (AML/MDS) in children. DNA was extracted from bone marrow slides of 292 AML/MDS patients. PCR amplification was used to assign GSTM1 and GSTT1 genotypes for cases and controls. Given that the frequency of the null genotype varies by ethnicity and that the majority of the cases were Caucasian, analyses were restricted to 232 white (non-Hispanic) cases and 153 Caucasian non cancer controls. The frequency of GSTM1 null was significantly increased in AML/MDS cases compared with controls [64 versus 47%; odds ratio (OR), 2.0 [95% confidence interval (CI), 1.3-3.1]; P = 0.001], whereas the frequency of GSTT1 null genotype in AML/MDS cases was not statistically different from controls. AML comprises biologically distinct subtypes, and a test for homogeneity revealed a statistically significant difference among subtypes (P = 0.04; df, 8) for GSTM1 only. In particular, there was an increased frequency of GSTM1 null genotypes in French-American-British groups M3 [82%; n = 22; OR, 5.1 (95% CI, 1.6-21.3)] and M4 [72%; n = 53; OR, 2.9 (95% CI, 1.4-6.0)]. We conclude that the GSTM1 null genotype is a significant risk factor for childhood AML, particularly French-American-British groups M3 and M4. This may indicate an important role for exogenous carcinogens in the etiology of childhood AML.
Child↗
Late outcomes after bone marrow transplant for aplastic anaemia.
Allogeneic transplantation is effective in reconstituting haemopoiesis in severe aplastic anaemia (SAA). We report long-term health-related outcomes in 37 children and young adults with SAA transplanted between 1975 and 1996. The median length of follow-up was 17 years (range, 4-25 years). Using a case-control design, late social and medical outcomes in transplant recipients were compared with 146 control subjects matched for gender and age. The majority of patients received an irradiation-containing preparative regimen. There were no significant differences in the self-rating of health status between transplant recipients and controls (P = 0.8), with 71% reporting their health status as excellent and 29% as good compared with 74% and 26% of controls. They demonstrate the same normal psychosexual function as their peers and have similar educational achievements and employment history. Transplant recipients and controls are equally likely to have held a job or be currently employed and there are no significant differences in their personal income (OR = 0.60, 95% CI = 0.11-3.37). Although transplant recipients have had problems related to health insurance policies, the majority have adequate health insurance coverage. There were no differences in chronic health problems between transplant recipients and control subjects, except for expected increases in cataracts, short stature in men, hypothyroidism and gonadal dysfunction. Using self-assessment, these transplant recipients indicated an excellent level of satisfaction and social integration, showing transplantation to be an effective long-term therapy for SAA.
Adolescent↗
Breast-feeding and risk of childhood acute leukemia.
BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.
Acute Disease↗
Population density and risk of childhood acute lymphoblastic leukaemia.
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Europe↗
Parental cigarette smoking and the risk of acute leukemia in children.
BACKGROUND: Studies of the relation between parental smoking and childhood leukemia have produced inconsistent results. In the largest case-control studies of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) conducted to date, the authors evaluated leukemia risk relative to parental self-report of cigarette smoking. METHODS: In telephone interviews in which a structured questionnaire was used, parents of 1842 ALL patients, 517 AML patients, and their matched controls were asked about their cigarette smoking habits before, during, and after the pregnancy with the index child. Risk of leukemia was examined by histologic type, age of the child at diagnosis, immunophenotype (for ALL), and French-American-British morphology group (for AML). RESULTS: The risk of ALL was not associated with the father's ever having smoked (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.90-1.20) or the mother's ever having smoked (OR = 1.04, 95% CI 0.91-1.19). Similarly, no significant risk of AML was observed for paternal (OR = 0.88, 95% CI 0.67-1.16) or maternal smoking (OR = 0.95, 95% CI 0.74-1.22). The relative risk of leukemia was not significantly different from the null for parental smoking in any time period during or around the index pregnancy, nor was it related to the number of cigarettes, the number of years of smoking, or the number of pack-years. A small number of sporadic, statistically significant associations were found, but overall there appeared to be no association between parental cigarette smoking and ALL or AML, or any subgroup of leukemia. CONCLUSIONS: Parental smoking while pregnant or exposure to cigarette smoke shortly after birth is unlikely to contribute substantially to the risk of childhood leukemia in North America.
Acute Disease↗
Marriage in the survivors of childhood cancer: a preliminary description from the Childhood Cancer Survivor Study.
BACKGROUND: The goal of this paper is to provide a preliminary description of the marital status for a large number of childhood cancer survivors participating in the Childhood Cancer Survivor Study (CCSS). PROCEDURE: This report includes children and adolescents (< 21 years of age) diagnosed with cancer between 1970 and 1986 at 25 oncology centers in the United States and Canada who survived at least 5 years from diagnosis. Self-reported data from 10,425 survivors are used in this preliminary descriptive summary. The proportion of survivors ever married and divorced/separated is compared to the U.S. population according to age-specific groups. The median age of the survivor population at diagnosis was 7 years and 26 years at the time martial status was ascertained. Excluded from this assessment are children < 15 years of age at the time of study, those whose martial status was unknown, and those married prior to diagnosis. Data for marital status of the U.S. population, as tabulated in the Bureau of Census 1995 Update, is used as a general comparison to the survivor population. RESULTS: Overall, 32% of the survivors reported being married or living as married, 6% being divorced or separated, 0% being widowed, and 62% having never been married. In general, compared to the U.S. population, survivors were less likely to have ever married, particularly females and whites, but, once married, were less likely to divorce/separate, again particularly females and whites. Black survivors were generally found to be more likely to have married, with males and blacks more likely to divorce/separate once married. Comparison of childhood tumor types suggested that survivors of CNS tumors, particularly males, were less likely to have ever married and more likely to divorce/separate compared to those with other cancer diagnoses and the general U.S. population. CONCLUSIONS: This interim evaluation of the CCSS cohort provided preliminary data describing a suggested decreased likelihood of marriage, which may be influenced by gender and/or race. These patterns must be confirmed within the entire CCSS cohort and comparisons made with an appropriate sibling comparison group before making final conclusions.
Adolescent↗
Family history of cancer in children and young adults with colorectal cancer.
BACKGROUND: Family history of colorectal cancer among adult patients has been reported in the literature. Although extremely rare in children, colorectal cancer in this population may represent a unique group in whom genetic factors play a significant etiologic role. The aim of the present study was to assess genetic contribution, as measured by family history, to the development of colorectal cancer in probands under 21 years of age at diagnosis. PROCEDURE: Detailed family histories were obtained from surviving patients or their parents. The risk [standardized incidence ratio (SIR)] of cancer in the relatives was calculated by comparing the observed and the expected incidence based on rates in the general population and person-years at risk. RESULTS: Twenty-five patients (median age at diagnosis 15 years) diagnosed with colorectal cancer at St. Jude Children's Research Center since 1964 or their surviving next of kin were available for interview. The 461 relatives contributed 18,908 person-years of follow-up. Statistically significant increased risk of colorectal cancer was present among all relatives (SIR = 6.0, 95% CI, 2.7-10.6), and the increased risk of colorectal cancer was confined to relatives of probands who were under 15 years of age at diagnosis (SIR = 10.0, 95% CI, 4.5-17.6). In addition, there was an excess of uterine/cervical cancer among all female relatives (SIR = 6.5, 95% CI, 3.2-10.9). CONCLUSIONS: The observed excess of colorectal cancer, in relatives of younger probands, suggests the need to examine these kindreds for genetic instability resulting from defects in mismatch repair genes to characterize further the patterns of risk observed.
Adolescent↗
Infant vaccinations and risk of childhood acute lymphoblastic leukaemia in the USA.
Previous studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia. Vaccination histories were compared in 439 children (ages 0-14) diagnosed with acute lymphoblastic leukaemia (ALL) in nine Midwestern and Mid-Atlantic states (USA) between 1 January 1989 and 30 June 1993 and 439 controls selected by random-digit dialing and individually matched to cases on age, race and telephone exchange. Among matched pairs, similar proportions of cases and controls had received at least one dose of oral poliovirus (98%), diphtheria-tetanus-pertussis (97%), and measles-mumps-rubella (90%) vaccines. Only 47% of cases and 53% of controls had received any Haemophilus influenzae type b (Hib) vaccine (relative risk (RR) = 0.73; 95% confidence interval (CI) 0.50-1.06). Although similar proportions of cases (12%) and controls (11%) received the polysaccharide Hib vaccine (RR = 1.13; 95% CI 0.64-1.98), more controls (41%) than cases (35%) received the conjugate Hib vaccine (RR = 0.57; 95% CI 0.36-0.89). Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL, our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia. Further studies are needed to confirm this association and, if confirmed, to elucidate the underlying mechanism.
Adolescent↗
Seasonal variations in the diagnosis of childhood cancer in the United States.
Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of 20,949 incident cancer cases diagnosed in the USA from 1 January 1989 through 31 December 1991 were available for analyses. Diagnosis-specific malignancies available for evaluation included ALL, acute myeloid leukaemia (AML), Hodgkin's disease, NHL, rhabdomyosarcoma, neuroblastoma, retinoblastoma, osteosarcoma, Wilms' tumour, retinoblastoma, Ewings' sarcoma, central nervous system (CNS) tumours and hepatoblastoma. Overall, there was no statistically significant seasonal variation in the month of diagnosis for all childhood cancers combined. For diagnosis-specific malignancies, there was a statistically significant seasonal variation for ALL (P = 0.01; peak in summer), rhabdomyosarcoma (P = 0.03; spring/summer) and hepatoblastoma (P = 0.01; summer); there was no seasonal variation in the diagnosis of NHL. When cases were restricted to latitudes greater than 40 degrees ('north'), seasonal patterns were apparent only for ALL and hepatoblastoma. Notably, 33% of hepatoblastoma cases were diagnosed in the summer months. In contrast, for latitudes less than 40 degrees ('south'), only CNS tumours demonstrated a seasonal pattern (P = 0.002; winter). Although these data provide modest support for a summer peak in the diagnosis of childhood ALL, any underlying biological mechanisms that account for these seasonal patterns are likely complex and in need of more definitive studies.
Adolescent↗
Indoor residential radon exposure and risk of childhood acute myeloid leukaemia.
Exposure to radon has been identified as a risk factor for lung cancer in uranium miners, but evidence of adverse health effects due to indoor radon exposure is inconsistent. Ecological studies have suggested a correlation between indoor radon levels and leukaemia incidence. We evaluated the risk associated with indoor residential radon exposure within a larger interview-based case-control study of risk factors for childhood acute myeloid leukaemia (AML). A total of 173 cases and 254 controls met the eligibility criteria, and information was collected through telephone interviews with parents and analysis of alpha-track radon detectors placed in the home for a period of 1 year. No association was observed between radon exposure and risk of AML, with adjusted odds ratios of 1.2 (95% confidence interval (CI) 0.7-1.8) for 37-100 Bq m(-3) and 1.1 (95% CI 0.6-2.0) for > 100 Bq m(-3) compared with < 37 Bq m(-3). Although there was an inverse association between radon level and AML risk among children < 2 years at diagnosis, among children > or = 2 years, AML risk was increased among those with higher radon exposure. The observed association after age 2 is most likely due to chance. Overall, there was no association between residential radon and risk of childhood AML.
Acute Disease↗
Epidemiology of leukemia and lymphoma.
The causes of acute leukemia and lymphomas are still largely unknown. These malignancies account for approximately 6% of cases of cancer in the US population, and active research efforts are now underway to define etiologically important genetic or environmental factors for these conditions. Recent epidemiologic studies have focused on international variations, secular trends, genetic syndromes, familial aggregation, chromosomal abnormalities, environmental exposures, and unique subgroups defined either demographically or biologically.
Humans↗
Residential exposure to magnetic fields: an empirical examination of alternative measurement strategies.
OBJECTIVES: To investigate the impact of measuring a single home then imputing information from another home among subjects who lived in two homes in a subset of the National Cancer Institute/Children's Cancer Group (NCI/CCG) investigation of residential exposure to magnetic fields and risk of childhood leukaemia. METHODS: Each subject's summary time weighted average (TWA) exposure was derived from measurements of two homes, weighted by the fraction of the reference period lived in the residence. The three cost efficient field work strategies examined were measuring: (a) the longer lived in home; (b) the currently lived in home; and (c) the former lived in home. Two different methods were used for imputing the missing values: (a) control mean imputation, (b) status specific mean imputation. The subject's summary exposure to magnetic fields estimated with each approach was compared with the subject's TWA calculated from measurements in both homes. The association between estimated exposure to magnetic fields and the risk of leukaemia under different approaches was examined with unconditional logistic regression analysis. RESULTS: The Pearson correlation coefficient between the two measurements within subjects was 0.31 (p < 10(-4), indicating a lack of independence of measurements. Differences were found between mean exposures in current and former homes of cases, and between longer and shorter lived in homes of controls. All methods with measurements from one of the homes in conjunction with imputation of measurements for the second home led to marked attenuation of risk estimates at the highest exposure category, particularly when measurements from current homes were used and those from former homes were imputed. CONCLUSION: Results argue against attempting to estimate lifetime magnetic field exposure from imputed values derived from current residences to fill in gaps caused by unmeasured residences previously lived in.
Bias↗
Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring.
Parental exposure to hydrocarbons at work has been suggested to increase the risk of childhood leukemia. Evidence, however, is not entirely consistent. Very few studies have evaluated the potential parental occupational hazards by exposure time windows. The Children's Cancer Group recently completed a large-scale case-control study involving 1842 acute lymphocytic leukemia (ALL) cases and 1986 matched controls. The study examined the association of self-reported occupational exposure to various hydrocarbons among parents with risk of childhood ALL by exposure time window, immunophenotype of ALL, and age at diagnosis. We found that maternal exposure to solvents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.3-2.5] and paints or thinners (OR, 1.6; 95% CI, 1.2-2.2) during the preconception period (OR, 1.6; 95% CI, 1.1-2.3) and during pregnancy (OR, 1.7; 95% CI, 1.2-2.3) and to plastic materials during the postnatal period (OR, 2.2; 95% CI, 1.0-4.7) were related to an increased risk of childhood ALL. A positive association between ALL and paternal exposure to plastic materials during the preconception period was also found (OR, 1.4; 95% CI, 1.0-1.9). The ALL risk associated with parental exposures to hydrocarbons did not vary greatly with immunophenotype of ALL. These results suggest that the effect of parental occupational exposure to hydrocarbons on offspring may depend on the type of hydrocarbon and the timing of the exposure.
Adolescent↗
Epidemiology of osteosarcoma and Ewing's sarcoma in childhood: a study of 305 cases by the Children's Cancer Group.
BACKGROUND: The Children's Cancer Group conducted a case-control study to determine the role of a broad range of environmental and familial factors in the etiology of Ewing's sarcoma and osteosarcoma in children. These factors included radiation exposure and, for children with osteosarcoma, parental exposure to beryllium. METHODS: The parents of 152 children with osteosarcoma and 153 children with Ewing's sarcoma were interviewed by telephone. Controls were obtained by random digit dialing and were matched to cases by age and race. RESULTS: Female osteosarcoma patients had earlier onset of breast development (age 11.4 vs. 11.8 years, P=0.03) and menarche (age 12.1 vs. 12.5 years, P=0.002) but no significant differences in growth, whereas male osteosarcoma patients were similar in age at the onset of secondary sexual characteristics but reported significantly less weight gain during their growth spurt (6.6 vs. 11.7 kg, P=0.003). For children with Ewing's sarcoma, the growth spurt began earlier (age 12.1 vs. 12.7 years, P=0.12) and resulted in less weight and height gain (5.2 vs. 9.7 kg, P=0.002, and 10.2 vs. 12.7 cm, P=0.02, respectively) for males, but no differences were observed among females. For factors not related to growth and development (including a wide range of occupational, medical, and household exposures), there was little evidence of an etiologic role with respect to either tumor type. CONCLUSIONS: Differences between cases and controls with respect to growth and development showed no consistent pattern. This study did not identify any important risk factors for either type of childhood bone tumor.
Adolescent↗
Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.
BACKGROUND: Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. METHODS: Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. RESULTS: Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. CONCLUSIONS: In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.
Carcinogens, Environmental↗
Smoking in adult survivors of childhood acute lymphoblastic leukemia.
BACKGROUND: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction. The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls. METHODS: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls. Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects. Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking. RESULTS: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant. There were no interactions between survivor status and either demographic or psychological features on smoking behavior. CONCLUSIONS: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls.
Actuarial Analysis↗