Parental occupational exposures to electromagnetic fields and radiation and the incidence of neuroblastoma in offspring.

We examined parental occupational exposures to electromagnetic fields and radiation and the incidence of neuroblastoma in offspring. Cases were 538 children diagnosed with neuroblastoma between 1992 and 1994 in the United States or Canada. Age-matched controls were selected by random-digit dialing. Occupational exposures to electrical equipment and radiation sources were classified by an industrial hygienist, and average exposures to extremely low frequency magnetic fields were estimated using a job exposure matrix. Maternal exposure to a broad grouping of sources that produce radiofrequency radiation was associated with an increased incidence of neuroblastoma (odds ratio = 2.8; 95% confidence interval = 0.9-8.7). Paternal exposure to battery-powered forklifts was positively associated with neuroblastoma (odds ratio = 1.6; 95% confidence interval = 0.8-3.2), as were some types of equipment that emit radiofrequency radiation (odds ratios congruent with 2.0); however, the broad groupings of sources that produce ELF fields, radiofrequency radiation, or ionizing radiation were not associated with neuroblastoma. Paternal average extremely low frequency magnetic field exposure >0.4 microTesla was weakly associated with neuroblastoma (odds ratio = 1.6; 95% confidence interval = 0.9-2.8), whereas maternal exposure was not. Overall, there was scant supportive evidence of strong associations between parental exposures in electromagnetic spectrum and neuroblastoma in offspring.

Hormone and fertility drug use and the risk of neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group.

Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration.

Methodologic approaches to studying environmental factors in childhood cancer.

Little is known about environmental causes of childhood cancer. This is probably due to the relative rarity of cancer in children. In the United States, cancer incidence in adults is over 20 times greater than cancer incidence in children. The situation is compounded by the fact that two groups of cancers, leukemias and brain and spinal tumors, account for half of all childhood cancers. The rarity of childhood cancer renders the conduct of most cohort studies infeasible. The majority of studies assessing potential environmental risk factors for childhood cancers have been case-control studies, which are highly efficient for studying rare diseases. Case-control studies of childhood cancers have been greatly facilitated by using cooperative clinical trial groups for case identification. The national studies that have emerged utilize random-digit telephone dialing and telephone interviewing as feasible and economic means of identifying and interviewing controls. Other approaches such as descriptive epidemiology, ecologic studies, and studies of cancer clusters have proven to be disappointing in elucidating environmental causes of childhood cancer. Descriptive and ecologic studies provide no information on specific exposures of study subjects; rather, they use population levels as surrogates for individual exposure. Studies of cancer clusters have also proven to be disappointing. Although there are numerous difficulties in conducting research on the causes of childhood cancer, these difficulties can be remedied by using carefully designed and conducted studies. It should be remembered that the epidemiologic approach is probably the most likely research venue for uncovering environmental causes of childhood cancer.

Impact of free vaccine and insurance status on physician referral of children to public vaccine clinics.

CONTEXT: Concerns about financial barriers to vaccination led to the development of the Vaccines for Children (VFC) program, which provides free vaccines to states for children who are uninsured, Medicaid eligible, or Native American or Native Alaskan. OBJECTIVE: To understand the effect of economic factors on physician likelihood of referring children to public vaccine clinics for immunizations and to evaluate the VFC program. DESIGN: A standardized survey was conducted in 1995 by trained personnel using computer-assisted telephone interviewing. SETTING AND PARTICIPANTS: A stratified random sample of family physicians, pediatricians, and general practitioners younger than 65 years who were in office-based practices across the United States. MAIN OUTCOME MEASURES: Likelihood of referral of a child to a health department for vaccination by child's insurance status and by the physician's receipt of free vaccines. RESULTS: Of the 1769 physicians with whom an interviewer spoke, 1236 participated. Most respondents (66%) were likely to refer an uninsured child to the health department for vaccination, whereas only 8% were likely to refer a child who had insurance that covers vaccination. The majority (58%) of physicians reported differential referral based on insurance status. Among physicians who received free vaccine supplies from the VFC program or elsewhere, 44% were likely to refer an uninsured child whereas 90% of those not receiving free vaccine were likely to refer the same child (P<.001). In regression analysis, the receipt of free vaccine supplies accounted for 24% of the variance in the likelihood to refer an uninsured child for vaccination. CONCLUSIONS: Physicians receiving free vaccine supplies report being less likely to refer children to public clinics for vaccinations.

Barriers to measles and pertussis immunization: the knowledge and attitudes of Pennsylvania primary care physicians.

OBJECTIVES: To understand the causes of low childhood immunization rates, physicians were interviewed about their knowledge, attitudes, and self-reported immunization practices. METHODS: Trained interviewers conducted a standardized telephone survey of physicians. A random sample of Pennsylvania family physicians, pediatricians, and general practitioners younger than 65 years of age who were in office-based practices was selected from the combined listings of the American Medical Association and American Osteopathic Association. Physicians seeing > or = 5 patients per week under age 6 years, seeing a total of > or = 15 patients per week, and having > or = 50% primary care patients were eligible. Of 383 eligible physicians, 70% (268) responded. The questionnaire was designed using the Health Belief Model, immunization barriers, and input from practitioners in primary care, pediatric infectious disease, maternal/ child health, and preventive medicine. RESULTS: Respondents were more likely to refer to public vaccine clinics those children without insurance (P < .001) or with Medicaid (P < .001) than children with insurance. Almost all (> 90%) respondents thought that vaccine efficacy was high and that the likelihood of serious side effects was low. However, only 37% gave estimates that corresponded with the literature regarding the likelihood of an infant with pertussis to need hospitalization. Many respondents used invalid vaccine contraindications; for instance, 37% would not administer MMR to a boy whose mother was pregnant. Many respondents (21%) would not administer four vaccines simultaneously. CONCLUSIONS: If the Healthy People 2000 goal to eliminate indigenous cases of measles is to be achieved, free vaccine supplies and increased provider education are needed.

International patterns in the occurrence of Hodgkin's disease in children and young adult males.

It was reported over 20 years ago that there were distinct age-specific patterns of Hodgkin's disease incidence in countries with different levels of economic development, and that there was an inverse relationship between the incidence of Hodgkin's disease in children and young adults within countries. Such observations were important, leading to hypotheses on the possibly infectious aetiology of the disease. Since the initial report, diverging trends in the incidence of Hodgkin's disease in children and young adults have been observed, and data from a much larger number of countries and cancer registries have become available. This led us to reassess international age-related incidence patterns of Hodgkin's disease occurrence. Recent data show distinct differences in age-specific Hodgkin's disease incidence patterns in different geographic regions. In general, the United States (US) and European countries had the pattern of low childhood rates and high young adulthood rates. However, countries which are not part of the European Union (EU), mainly Baltic states and countries of central and eastern Europe, showed a variant of this pattern: similarly high young adult rates, but rates in children higher than those in the US and EU. Incidence-rate patterns for Latin American countries differed from those previously observed, with a shift towards patterns observed in more economically developed countries. Analysis of incidence data from earlier sources dating back to 1963 confirmed the original finding of an inverse association in incidence rates (c. 1963-1967) using a selected group of cancer registries, but not when all data were considered. This association has become weaker over the past 20 years. Using current incidence rates (1983-1987), no association between Hodgkin's disease rates in children aged 5 to 14 years (as well as 0 to 9 years) and young adults (20 to 34 years) was found.

Association of childhood rhabdomyosarcoma with neurofibromatosis type I and birth defects.

Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma whose cause is largely unknown. Reported risk factors include genetic alterations (e.g., p53 mutations, a defective gene at 11p15.5, or specific chromosomal translocation of t(2:13)), and parents' use of drugs around the time of conception. We present results from a national, case-control study of 249 RMS cases (170 males and 79 females) and 302 controls (196 males and 106 females). The cases, aged 0-20 years at diagnosis, were identified via the Intergroup RMS Study-III during 1982-1988. Controls were selected by random digit telephone dialing. As a supplement to the original study, information on genetic diseases and birth defects (BD) was collected from the subjects' parents by telephone interview. Fifty-six (22.5%) cases and 55 (18.2%) controls were reported to have genetic diseases or BD (odds ratio [OR] = 1.30,95% confidence interval [CI] = 0.85-2.02, P = .21). The case group had a significantly higher frequency of neurofibromatosis type I (NF1) than did the control group, i.e., five cases (2.0%) had NF1 vs. zero controls (P = .02). The case group also had a higher frequency of major BDs than did the control group (6.0% vs. 2.6%, OR = 2.36, 95% CI = 0.92-6.52, P = .05). However, this excess was only observed in males (7.6% vs. 2.6%, OR = 3.16, 95% CI = 1.02-10.41, P = .02). Among the 15 cases having both RMS and major BDs, six (40.0%) had both conditions in the same regional anatomic site: Two (13.3%) had both in the extremities, two (13.3%) in the genitourinary system, and two in the head and neck. These findings suggest that common genetic mechanisms or in utero exposures may be involved in the development of many childhood tumors and congenital abnormalities.

Risk factors for Wilms tumor. Report from the National Wilms Tumor Study.

BACKGROUND: Previous epidemiologic studies have indicated that several factors may be associated with an increased risk of Wilms tumor including paternal occupational exposures, maternal exposure during pregnancy to cigarettes, coffee or tea, oral contraceptives, hormonal pregnancy tests, hair-coloring products, maternal hypertension, vaginal infection during pregnancy, and higher birth weight of the child. The current study examines the nonoccupational risk factors using questionnaire data from a large national collaborative clinical trial. METHODS: Parents of 200 children registered with the National Wilms Tumor Study and 233 matched controls, identified using telephone random-digit dialing, completed a self-administered questionnaire about a variety of risk factors. RESULTS: As opposed to some previous studies, no association was found for mother's smoking during pregnancy (10+ cigarettes per day; odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.40-1.34), maternal consumption of coffee or tea during pregnancy (4+ cups per day; OR = 1.31; CI = 0.57-3.01), or hypertension during pregnancy (OR = 0.96; CI = 0.45-2.06). In addition, no association was found in this study for hormone exposure during pregnancy, hair dye use, vaginal infection during pregnancy, or high birth weight. A previously unreported association with a history of household insect extermination was found (OR = 2.16; CI = 1.24-3.75). CONCLUSIONS: In general, the study failed to confirm most of the previously reported maternal risk factors for Wilms tumor. Understanding the possible role of paternal exposures may be the best objective for further research on potential risk factors for Wilms tumor.

Parents' use of cocaine and marijuana and increased risk of rhabdomyosarcoma in their children.

Parents' use of marijuana and cocaine was evaluated in a national (United States) case-control study of childhood rhabdomyosarcoma (RMS). Subjects were 322 RMS cases, aged 0-20 years, from the Intergroup Rhabdomyosarcoma Study, and 322 matched controls identified by random-digit telephone dialing. Parents of subjects were interviewed by telephone using a structured questionnaire. Mothers' marijuana use during the year before their child's birth was associated with a 3.0-fold increased risk of RMS in the child (95% confidence interval [CI] = 1.4-6.5) and maternal cocaine use was associated with a 5.1-fold increased risk (CI = 1.0-25.0). Risk was increased 3.1-fold (CI = 1.4-6.7) with use of any recreational drug. Fathers' marijuana use was associated with a 2.0-fold increased risk (CI = 1.3-3.3), cocaine use with a 2.1-fold increased risk (CI = 0.9-4.9), and use of any recreational drug with a 2.0-fold (CI = 1.3-3.3) increased risk. Case mothers' cocaine use and both parents' marijuana use were associated with their children being diagnosed at a significantly younger age. It was not possible to determine whether cocaine and marijuana have independent effects, since use of the two drugs was materially correlated. Similarly, mothers' and fathers' use of these drugs was highly correlated. In summary, parents' marijuana and cocaine use during the year preceding their child's birth may increase, by twofold to fivefold, the risk of RMS in their children.

Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States.

In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.

Issues and problems in the conduct of epidemiologic research on chronic fatigue syndrome.

The epidemiologic research approach is perhaps most appropriate for initial studies of chronic fatigue syndrome since the syndrome is vaguely defined, scientific knowledge about it is limited, and an infectious etiology is suspected. Several priority needs appropriate for epidemiologic research are identified, including a refinement of diagnostic criteria; a greater understanding of the natural history of the syndrome; basic incidence, prevalence, and mortality statistics; information on whether asymptomatic cases exist; etiologic studies of possible heterogeneity of cases; investigations of clusters of cases; and determinations of whether patients with the syndrome have an increased risk of malignancy. Because of the lack of cogent etiologic hypotheses regarding the syndrome, case-control studies are identified as a high priority for research. The many difficulties encountered in conducting such research are discussed and approaches to dealing with these problems are suggested.

Epidemiology of HIV associated non-Hodgkin lymphoma.

The excess of NHL associated with HIV infection is well established. Clinically, HIV associated NHL is characterized by histological evidence of a high grade of malignancy, B cell origin, extensive extranodal involvement (most notably of the CNS) and poor prognosis. High grade B cell lymphoma or primary brain lymphoma in HIV infected individuals is considered diagnostic of AIDS by the Centers for Disease Control. The incidence of NHL among individuals with AIDS varies by subtype of lymphoma, age, sex, race and risk group. Younger individuals, males, whites and haemophiliacs are at higher risk than other groups. The incidence of HIV associated NHL is increasing. Because of the paucity of data on risk factors for this malignancy, the current possibilities for risk modification are limited to the prevention of HIV infection.

Are stressful life events risk factors for herpes zoster?

To determine if psychologically stressful life events are risk factors for herpes zoster, we conducted a case-control study of zoster and self-reported recent negative life events and major changes in spousal relationships. The subjects were 101 healthy community-dwelling cases of zoster and 101 healthy controls matched for age, sex, and race and generated by random digit dialing. The Geriatric Scale of Recent Life Events was administered to case and control subjects, and additional questions were asked regarding the perception of the life event. The results showed that case subjects experienced negative life events significantly more often than subjects in the control groups in the 2 months before zoster onset by analysis of discordant pairs (26 versus 10, odds ratio 2.60, 95% confidence interval [CI] 1.13, 6.27, P = .012), 3 months before (29 versus 11, odds ratio 2.64, 95% CI 1.20, 6.04, P = .007), or 6 months before (35 versus 16, odds ratio 2.00, 95% CI 1.04, 3.93, P = .012). The mean number of total life events was significantly higher in cases at 6 months before zoster (case means = 2.64, control means = 1.82, P = .008), but there were no significant differences at 2, 3, or 12 months before. There were no significant differences between case subjects and control subjects for spousal events, or any given single life event. In conclusion, we found that whereas patients with herpes zoster experienced the same kinds of life events in the year preceding the illness as did control subjects, recent events perceived as stressful were significantly more common among patients with zoster.(ABSTRACT TRUNCATED AT 250 WORDS)

Wilms' tumor and paternal occupation.

A case-control study was conducted to examine the relationship between Wilms' tumor and paternal occupational exposures. The case group consisted of 200 children diagnosed as having Wilms' tumor who were registered at selected National Wilms' Tumor Study institutions during the period June 1, 1984, to May 31, 1986. Disease-free controls were matched to each case using a random digit dialing procedure. The parents of cases and controls completed a self-administered questionnaire. There was no consistent pattern of increased risk for paternal occupational exposure to hydrocarbons or lead found in this study. However, certain paternal occupations were found to have an elevated odds ratio (OR) of Wilms' tumor, including vehicle mechanics, auto body repairmen, and welders. Offspring of fathers who were auto mechanics had a 4- to 7-fold increased risk of Wilms' tumor for all 3 time periods. The largest increased odds ratio for auto mechanics was in the preconception period [OR = 7.58; 95% confidence interval (CI) = 0.90-63.9]. Welders had a 4- to 8-fold increased odds ratio, with the strongest association during pregnancy (OR = 8.22; CI = 0.95-71.3). Although chance cannot be excluded as a possible explanation, association of Wilms' tumor with these occupations has been reported in previous studies. Further study is needed to provide data on the specific occupational exposures involved.

Survival of the older patient compared with the younger patient with Hodgkin's disease. Influence of histologic type, staging, and treatment.

Age as an independent risk factor for survival of Hodgkin's disease (HD) was investigated using data for the 6345 patients in the American College of Surgeons, Patterns of Care Study. Patients were divided into those 15 to 34 years of age, and those older than 50 years. Older patients had higher rates of advanced stage and B symptoms (e.g., Stage IVB, 19.7% compared with 7.7%) and significantly higher rates of poor prognosis histologic types, odds ratio (OR) = 3.7. The older population with clinical stage (CS) I and II disease was also less likely to have received any of the selected staging procedures, bone marrow biopsy, lymphogram, or laparotomy (OR = 4.48). The two populations were equivalently understaged when CS was compared with pathologic stage (PS). In each category the older patients were more likely to have received no therapy; for PS I and II disease the OR for older patients compared with the younger patient was 2.14. When stratified by PS, B symptom status, histologic type, and treatment the older patients continued to show poorer 5-year survival by the life-table method. The authors' hypothesis--that older patients equivalently staged and treated would have no significant difference in long-term survival--was not substantiated by the data. However, in the analyses in which corrections for the known risk factors were made, the difference in survival was not as great as that in the crude, unstratified data. This study, as well as other recent studies utilizing smaller numbers of patients, finds age an independent predictor of poorer survival in HD patients.

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.