Neuroblastoma and paternal occupation. A case-control analysis

The peak incidence of neuroblastoma during early infancy suggests that prezygotic or prenatal exposures to carcinogens could be implicated. Several recent epidemiologic studies have suggested an association between parental exposure to petrochemicals and ionizing radiation and the development of cancer in the offspring. This paper is a population-based case-control analysis of the birth certificate data of 157 children who died in Texas from neuroblastoma in 1964-1978 and 314 controls randomly selected from all live births in Texas. Children of fathers employed in occupations with electromagnetic field exposure were at significantly increased risk (odds ratio = 2.13). The odds ratio was 11.75 for children of fathers who reported themselves to be electronics workers (6 cases, 1 control).     

Childhood nervous system tumours: an assessment of risk associated with paternal occupations involving use, repair or manufacture of electrical and electronic equipment

Parental occupational exposures to chemical carcinogens have been associated with malignancies in offspring. Recent studies have raised the issue that electromagnetic fields may play a role in carcinogenesis. We conducted a population-based case-control study testing for an association between the occurrence of a nervous system tumour in a child and paternal employment at the time of the child's birth in occupations involving potential exposure to low frequency electromagnetic fields, primarily in the electrical and electronics industries. Birth certificate data, including parental occupation information, of 499 children who died in Texas from intracranial and spinal cord tumours were compared with 998 controls randomly selected from Texas livebirths. The odds ratio for paternal employment in industries involving potential electromagnetic field exposure was 1.6 (p less than 0.07). A risk of 3.5 (p less than 0.05) was detected for fathers who were electricians. The additional presence of chemical exposures in these diverse occupations and industries must also be considered.     

Childhood nervous system tumors--an evaluation of the association with paternal occupational exposure to hydrocarbons

Paternal occupational exposures to hydrocarbons have been associated with childhood nervous system cancer, but study results have not been consistent. This population-based case-control study was designed to examine this association using a large sample size to increase the precision of risk estimates. The birth certificates of 499 children who died in Texas from intracranial and spinal cord tumors were compared with 998 control certificates randomly selected from all Texas live births. Information on parental job title and industry at the time of birth was obtained from the birth certificates. No significant associations were identified for the dichotomized variable of all hydrocarbon-related occupations combined, as variously defined in previous studies, or for most of the specific jobs affiliated with exposures to hydrocarbons. Significant, relatively stable odds ratios (OR) were found for printers and graphics arts workers (OR = 4.5; 95% confidence interval (CI) = 1.4-14.7) and chemical and petroleum workers with high exposure levels (OR = 3.0; CI = 1.1-8.5). A discussion of the biases involved in this type of study design is presented.     

An epidemiologic case-control study of central nervous system tumors in children and parental occupational exposures

A population-based case-control study was conducted with 338 patients less than 15 years of age who were diagnosed with a primary tumor of the central nervous system from January 1968 through December 1977 in 53 contiguous New York counties. The study also included 676 controls who were selected from the birth certificate files of the New York State Department of Health. Parental occupational exposures at the time of each child's birth and at the time of tumor diagnosis were derived from maternal interviews. The current data set failed to show any consistent association between childhood central nervous system tumor risk and paternal occupational exposures to hydrocarbons or to electromagnetic fields, or employment in the aerospace industry or pulp and paper manufacturing. Findings for occupational exposures to ionizing radiation were also inconsistent. A positive association was observed between central nervous system tumor risk and paternal exposures to ionizing radiation based on industrial codes. Odds ratios ranged from 1.71 to 2.15. This association was not observed when paternal occupational titles were used to define exposure (range of odds ratios, 1.01-1.10). Maternal exposures to ionizing radiation were not related to risk regardless of the classification scheme used.     

Association of childhood leukemia with maternal age, birth order, and paternal occupation. A case-control study

Previous investigations have drawn conflicting conclusions concerning the association between childhood leukemia and maternal age, birth order, socioeconomic status, and paternal occupation. In this study, 255 childhood leukemia cases diagnosed in California between 1975 and 1980 were individually matched with two living controls on the basis of sex, date of birth, and county of birth. Data were derived from subjects' birth certificates. Socioeconomic status and paternal benzene exposure were determined from the paternal occupation stated on the birth certificate. Hispanics and males were overrepresented in the case group. Cases were also less likely to be of birth order one. No difference was found between case and control groups for maternal age or paternal occupation. Analyses with stratification on age, sex, and leukemia cell type are reported.     

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.     

An exploratory investigation of suicide and occupational exposure

This exploratory study evaluated the association between suicide and occupational exposure to electromagnetic fields, pesticides, and hydrocarbon solvents. The study population comprised 11,707 suicide deaths and 132,771 eligible controls identified from United States death certificate files for the years 1991 and 1992. Exposure assignment was based on job title reported on the death certificates. Exposure to electromagnetic fields and pesticides was weakly associated with suicide risk, while little evidence for an increased risk was seen for hydrocarbon solvents. The association for electromagnetic field exposure was highest for suicide between the ages 20 and 35 (odds ratio; OR = 1.5), while the highest risk of suicide for pesticide exposure was seen between the ages of 35 and 49 years (OR = 1.5). Further investigation to replicate these findings seems warranted, using higher quality occupational data.     

Paternal occupational lead exposure and congenital malformations.

STUDY OBJECTIVE--The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. DESIGN--The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. SUBJECTS--Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. MEASUREMENTS AND MAIN RESULTS--Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. CONCLUSIONS--Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.     

Agricultural pesticides and risk of childhood cancers

Agricultural pesticide applications have the potential for significant drift beyond the target spray area and may result in exposure to non-farming residents in surrounding communities. Using geographic information system (GIS) methods, 1778 childhood cancer cases and 1802 controls born in Texas between 1990 and 1998 were assigned probable agricultural pesticide exposure based on proximity of birth residence to crop fields. Multivariate modeling was used to estimate odds ratios and 95% confidence intervals for selected cancers. For most childhood cancers, we found no evidence of elevated risk associated with residential proximity at birth to cropland. There was an overall pattern of increased risk for germ-cell tumors but the odds ratios were based on few number of exposed cases. There was also some indication of increased risk for non-Hodgkin lymphoma (NHL) and Burkitt lymphoma, but point estimates were imprecise and not statistically significant. Previous studies have assessed pesticide exposure primarily based on parental occupational history or household use, while our focus was on agricultural pesticides and so may represent a different array of chemical agents occurring at lower doses.     

Adjusting for multiple-misclassified variables in a study using birth certificates

PurposeBirth certificates are a convenient source of population data for epidemiologic studies. It is well documented, however, that birth certificate data can be highly inaccurate. Nonetheless, studies based on birth certificates are routinely analyzed without accounting for sources of data errors. We focused on the association between maternal cigarette smoking and cleft lip and palate based on birth certificate data.MethodsWe adjusted odds ratio estimates simultaneously for exposure and outcome misclassification. We also calculated odds ratios adjusted for exposure misclassification only and outcome misclassification only.ResultsAdjustment for both maternal smoking during pregnancy and clefting resulted in adjusted odds ratios that ranged from less than 1.0 to much greater than the unadjusted estimate of 1.16, with most adjusted estimates outside of the 95% confidence limits (1.01, 1.33).ConclusionsBecause of the potentially large impact of birth certificate classification errors, we suggest that inferences from these or similar records employ quantitative methods for incorporating uncertainties caused by data errors.     

Isoniazid Prophylaxis and BCG Vaccination in the Control of Tuberculosis

Proxy exposure measures and readily available data from the Wisconsin Cancer Reporting System were used to contrast 167 osteosarcoma cases with 989 frequency-matched cancer referents reported during 1979–1989. Differences in potential exposure to water-borne radiation and fluoridated drinking water, population size for the listed place of residence, and seasonality were assessed. An association was found between osteosarcoma and residence in a population of less than 9 000 (odds ratio = 1.6, 95% confidence interval = 1.1–2.4). In addition, an association between month of birth (May through July versus other months of birth) and osteosarcoma among individuals who were less than 25 y of age (odds ratio = 1.9, 95% confidence interval = 1.1–3.4). Overall, no association was found between potential exposure to fluoridated drinking water and osteosarcoma (odds ratio = 1.0, 95% confidence interval = 0.6–1.5). The association between osteosarcoma and water-borne radiation was weak and was not significant statistically (odds ratio = 1.5, 95% confidence interval = 0.8–2.8).     

Occupational lead exposure and strabismus in offspring: a case-control study

The authors conducted a population-based case-control study to investigate the association between strabismus and parental occupational lead exposure. Cases were children diagnosed with nonrestrictive strabismus between 1985 and 1986 at Baltimore, Maryland-area pediatric ophthalmology practices and clinics (n = 377). Controls were matched for age and hospital of birth (n = 377). Jobs held by parents were assessed for lead exposure by industrial hygienists. The time window for lead exposure was defined as the period from conception through age 9 months. The unadjusted odds ratio for maternal lead exposure and the esotropic form of strabismus was 2.6 (95% confidence interval (CI) 0.4-27). Unadjusted odds ratios for paternal occupational lead exposure and esotropia were 1.0 (95% CI 0.5-2.1) for low exposure, 2.1 (95% CI 0.9-5.3) for moderate exposure, and 1.2 (95% CI 0.4-3.3) for high exposure. The study results suggest the possibility of a weak association between paternal lead exposure and strabismus in offspring.     

Prevalence and Risk Factors for Adult Paternity Among Adolescent Females Ages 14 through 16 Years

To investigate sociodemographic factors associated with adolescent females ages 14–16 years having children fathered by males age 20 years or older and identify differences in correlates across rural, urban, and border areas. The method section was a cross-sectional study using Texas birth record data. From 2000 through 2004, there were 29,186 births to adolescent females aged 14–16 years with valid paternal age. Prevalence of and adjusted odds of paternal age of 20 years or older were identified by paternal and maternal factors. The Results section Having both parents born outside of the U.S. was associated with a 5.29 (95% CI: 4.82, 5.80) times increase in the odds of paternal age of 20 years or older as compared to having both parents born in the U.S. Parental place of birth was associated with greater odds of paternal age of 20 years or older in urban areas compared to rural or border areas. Compared to those with average or high educational attainment relative to age, low educational attainment relative to age was associated with an increase in the odds of paternal age of 20 years or older. This association was present whether maternal or paternal educational attainment was low relative to age. Messages are needed to help adolescent females avoid pregnancy with adult males. In addressing this specific prevention challenge, it is important to consider maternal/paternal place of birth and its association with adolescent births with adult males.     

Paternal age and sporadic neurofibromatosis 1: A case-control study and consideration of the methodologic issues

Sporadic neurofibromatosis 1 (NF1) occurs in the absence of a family history of the disease and usually results from a new mutation in the germ cell of one of the parents, most commonly the father. Older paternal age may increase the risk for a new germinal NF1 mutation, but the results of studies to address this question conflict. We investigated paternal age in sporadic NF1 by using a case-control study design. Patients who were seen at two specialty NF clinics in Houston, Texas, born between 1970 and 1992 and living in the Houston area and surrounding counties, were studied. Birth certificates with information on the father were found for 89 cases. For each case, two birth certificates were chosen at random from the same year and county of birth. In this way, the control group of 178 individuals was formed. Fathers of patients with NF1 were 1.5 years older than fathers of control subjects at the birth of the child, but the difference was only of borderline statistical significance (P = 0.07). This paternal age difference was not changed by adjustment for socioeconomic status or maternal age. These and previous data are consistent with either a small paternal age effect in sporadic NF1 or a bias such as that resulting from the selection of cases and/or controls. Genet. Epidemiol. 14:507–516,1997. © 1997 Wiley-Liss, Inc.     

Parental exposure to medical radiation and neuroblastoma in offspring

Previous studies have suggested an association between parental medical radiation exposure and increased incidence of certain childhood cancers. We investigated the relationship between medical radiation and risk of neuroblastoma in offspring using data from a North American case-control study. Cases were children diagnosed with neuroblastoma from 1 May 1992, to 30 April 1994, at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control per case was selected using random-digit dialling. Telephone interviews were conducted with parents to collect data on any medical radiation examinations and treatments in the 2 years before conception or during pregnancy. We included 500 maternal and 339 paternal matched pairs. Overall, no association was found between maternal exposure to radiation and neuroblastoma risk (odds ratio [OR] = 1.0; 95% confidence interval [CI]: 0.7, 1.3). Analysis of maternal exposure by specific anatomical site showed no association for gonadal sites [OR = 1.0; 95% CI = 0.5, 2.0]. Little association was found with paternal radiation exposure [OR = 1.2; 95% CI = 0.8, 1.8]. No consistent exposure-response gradient was found based upon the number of maternal or paternal medical radiation examinations. The data presented here, coupled with the lower radiation doses currently used, indicate that any further study of this question will require larger studies with improved exposure assessment.     

Parental occupational exposure to pesticides and childhood germ-cell tumors

In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring.     

Neuroblastoma and parental occupation

A matched case-control study of neuroblastoma investigated parental occupational risk factors. Cases diagnosed in 1970-1979 were identified through tumor registries in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone exchange. Parents of 104 matched pairs were interviewed by telephone. In contrast to results of a previous study, no significant associations were noted for paternal employment in a job cluster of occupations in electricity, electronics, insulation, utility, and printing; in jobs with electromagnetic field exposure; or in jobs as workers in electronics. Six cases and one control, however, had a father or mother who worked in electrical or electronic products assembly.     

Paternal occupation and neural tube defects: a case-control study based on the Oxford Record Linkage Study register

Certain paternal occupations and related exposures have been suggested as possible risk factors for neural tube defects (NTD). We analysed data collected as part of a case-control study to investigate the relationship between paternal occupational exposures and NTD. Cases were 694 NTD-affected pregnancies diagnosed between 1970 and 1987 in Oxfordshire or West Berkshire, England. Controls were randomly selected from a computerised maternity database individually matched to cases on maternal year of birth and year of index pregnancy. Data on paternal occupation were abstracted from hospital antenatal records. Associations between paternal occupational exposures and NTD were assessed using odds ratios adjusted for maternal year of birth, year of index pregnancy, gender of baby, multiplicity of birth and number of previous obstetric events. Statistically significant positive associations were observed for paternal occupational exposure to agrochemicals and animals. Analysis by occupational title revealed that more case than control fathers were farmers, gardeners and butchers. Statistically significant negative associations were seen for paternal occupational exposure to inhaled hydrocarbons and metal-working oil mists. The findings from this population-based study for paternal agricultural and animal-related occupations overlap and have been previously observed. The apparent protective effects of fathers working with inhaled hydrocarbons and metal-working oil mists have not been previously described. No underlying biological mechanisms have been identified, therefore other explanations cannot be excluded.     

Maternal medication use and neuroblastoma in offspring

The association between a mother's use of specific medications during pregnancy and lactation and neuroblastoma in her offspring was evaluated in a case-control study. Newly diagnosed cases of neuroblastoma (n=504) in the United States and Canada were identified between 1992 and 1994 at 139 hospitals affiliated with the Pediatric Oncology Group or the Children's Cancer Group clinical trial programs. One age-matched control was sampled from the community of each case by means of random digit dialing. Exposure information was ascertained retrospectively from mothers in a structured telephone interview. Odds ratios were estimated using conditional logistic regression, with adjustment for maternal sociodemographic factors. The results did not support an association between neuroblastoma and maternal exposure to diuretic agents, antiinfective agents, estrogens, progestins, sedatives, anticonvulsant drugs, or drugs that may form N-nitroso derivatives. Mothers of cases were more likely to report using medications containing opioid agonists while they were pregnant or nursing than were mothers of controls (odds ratio=2.4, 95% confidence interval: 1.3, 4.3). Specifically, more mothers of cases reported using medications containing codeine while pregnant or nursing than did mothers of controls (odds ratio=3.4, 95% confidence interval: 1.4, 8.4). This preliminary finding may be due to bias, confounding, or chance, and additional studies are needed for confirmation.