Childhood exposure to ionizing radiation to the head and risk of schizophrenia

While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.     

An aetiological study of 290 XXY males,with special reference to the role of paternal age

Summary Data on 290 non-mosaic 47,XXY males have been analysed for possible associations with parental ages at birth, season of birth, sex ratio among sibs, and twinning. Comparison with matched population controls revealed a highly significant association with parental age, which was fully explained by dependence on maternal age and maternal age alone. The maternal age effect was determined with greater precision than in an earlier study of the same material, in which siblings were used as controls, and was estimated to result in an increased risk of between 5% and 10% per annum (p.a.). The estimated independent effect of paternal age, after fitting maternal age, was marginally (but not significantly) negative, and excluded an increased risk in excess of 3% p.a. Paternal age therefore appears to have little if any independent significance in the aetiology of 47,XXY. After correcting for seasonal variations in the population birth rate and smoothing, there was a peak of XXY births in March and a trough in November. Though not statistically significant, the pattern resembled that reported in previous studies, and was similar for both younger and older mothers. The twinning rate for both the XXYs and their sibs, and the sex ratio among the latter, were close to the corresponding population values.     

Esophagus cancer and radiation exposure due to nuclear test fallout: an analysis based on the data of the Semipalatinsk historical cohort, 1960-1999

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.     

Fetal dose assessment for the offspring of the Techa Riverside residents

Massive releases of fission products from the plutonium facility Mayak (Southern Urals, Russia) resulted in the contamination of the Techa river and its floodlands (1949–1956). The results of long-term studies of exposure populations have been used for different purposes of retrospective dosimetry. The riverside residents were exposed via various pathways and their progeny were exposed in utero both to external radiation and to internal radiation from radionuclides ingested by the mothers prior to conception and during pregnancy. Fetal doses due to ⁹⁰Sr from the maternal skeleton were estimated and compared with doses from other pathways. Individual red bone marrow (RBM) doses to the late fetuses were calculated on the basis of ⁹⁰Sr contents measured in the maternal skeleton and the ⁹⁰Sr transfer coefficients (TC) to the fetal skeleton were determined on the basis of the Techa river data. Two values of TC were assumed depending on the mothers’ maturation status in the period of maximum releases: TC=0.2 for group 1 (adulthood of mothers in 1950) and TC=0.02 for group 2 (mothers not yet in menarche age in 1950). Fetal doses in both groups that resulted from the different TC values varied by a factor of about 5–8. Furthermore, the fetal RBM doses due to ⁹⁰Sr from the maternal skeleton were found to depend on the distances from the site of release and the time after major ⁹⁰Sr intake. The average fetal RBM doses in the population of the upper, middle and lower Techa riverside regions were close to the ratio 3:2:1 and 20 years after the onset of contamination, the fetal doses have decreased by a factor of about 3–5. The distance from the site of release determined the relative contribution of different pathways to the fetal dose. For the settlements that are located closest to the site of release, the external exposure was of major concern up to the date of evacuation. For the non-evacuated settlements, the contribution of internal doses was higher and after 1956, external exposure is assumed to be negligible. From 1956 on, ⁹⁰Sr that has been transferred from the maternal skeleton was practically the single source of in utero exposure. Received: 8 December 2000 / Accepted: 1 July 2001     

The application and adaptation of ICRP internal dosimetry models to the calculation of bone marrow tissue doses from 90Sr for epidemiological studies of Techa River populations

The operation of the Mayak Production Association in the Southern Urals region of Russia, resulted in releases of large amounts of radioactive effluent into the Techa River during the period 1949-1956. The residents of the riverside communities were thus exposed to both external radiation, and internal radiation following ingestion of contaminated water and foodstuffs. One of the most important radionuclides for internal exposure was 90Sr. This paper gives a brief overview of the models provided by International Commission on Radiological Protection (ICRP), which are of interest for assessing internal doses from 90Sr. The application of these models to the calculation of red bone marrow doses for the fetus and infant from 90Sr intakes by the mother and the infant is illustrated by an example. A hypothetical individual born in 1951 is used as an example for dose calculations. The following doses due to intakes of 90Sr are taken into account: received in utero due to maternal intakes during pregnancy; received after birth from 90Sr accumulated by the fetus in utero; from intakes in breast milk; from intakes in the infant's diet after weaning. It is shown that doses to the fetus following maternal ingestion and subsequent transfer to the fetus via the placenta dominate the doses received for this particular individual for the first two years of life. Doses to the infant from intakes in breast milk are substantially lower but do make significant contributions to total doses in the first two years after birth. By about the age of two years residual 90Sr from placental transfer still contributes about the same dose as do intakes by the infant, but in later years doses from intakes by the infant dominate.     

Behavior and food consumption pattern of the population exposed in 1949�C1962 to fallout from Semipalatinsk nuclear test site in Kazakhstan

The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the US National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to deposition of radioactive fallout from nuclear testing conducted by the Soviet Union at the Semipalatinsk Nuclear Test Site in Kazakhstan between 1949 and 1962. The study subjects included individuals of both Kazakh and Russian origin who were exposed during childhood and adolescence. An initial dose reconstruction used for the risk analysis of Land et al. (Radiat Res 169:373?C383, 2008) was based on individual information collected from basic questionnaires administered to the study population in 1998. However, because data on several key questions for accurately estimating doses were not obtained from the 1998 questionnaires, it was decided to conduct a second data collection campaign in 2007. Due to the many years elapsed since exposure, a well-developed strategy was necessary to encourage accurate memory recall. In our recent study, a focus group interview data collection methodology was used to collect historical behavioral and food consumption data. The data collection in 2007 involved interviews conducted within four-eight-person focus groups (three groups of women and one group of men) in each of four exposed villages where thyroid disease screening was conducted in 1998. Population-based data on relevant childhood behaviors including time spent in- and outdoors and consumption rates of milk and other dairy products were collected from women??s groups. The data were collected for five age groups of children and adolescents ranging from less than 1?year of age to 21?years of age. Dairy products considered included fresh milk and other products from cows, goats, mares, and sheep. Men??s focus group interviews pertained to construction materials of houses and schools, and animal grazing patterns and feeding practices. The response data collected are useful for improving estimates of thyroid radiation dose estimates for the subjects of an ongoing epidemiological study.     

Possible Relationships between Plasma Glutathione Levels and Cytogenetic Indices in Peripheral Blood Lymphocytes of Children Exposed to Low Doses of Radiation

An analysis of correlations between cytogenetic indices in lymphocytes and levels of reduced glutathione in the plasma of peripheral blood in children born after the Chernobyl accident is presented. The studied systems in the child population demonstrated different responses to low-level radiation of their mothers living in conditions of radionuclide contamination (1–20 Ci/km² of ¹³⁷Cs). Low doses of radiation accumulated by mothers (below 30 cSv) proved to have a more pronounced effect on the studied systems in children as compared to high doses (from 30 to 60 cSv).     

Hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers

A single accidental event such as the fallout released from the Chernobyl reactor in 1986 can expose millions of people to non-natural environmental radiation. Ionizing radiation increases the frequency of germline mutations in experimental studies, but the genetic effects of radiation in humans remain largely undefined. To evaluate the hereditary effects of low radiation doses, we compared the minisatellite mutation rates of 155 children born to Estonian Chernobyl cleanup workers after the accident with those of their siblings born prior to it. All together, 94 de novo paternal minisatellite mutations were found at eight tested loci (52 and 42 mutants among children born after and before the accident, respectively). The minisatellite mutation rate was nonsignificantly increased among children born after the accident (0.042 compared to 0.036, OR 1.33, 95% CI 0.80-2.20). Furthermore, there was some indication of an increased mutation rate among offspring born after the accident to workers who had received doses of 20 cSv or above compared with their siblings born before the accident (OR 3.0, 95% CI 0.97-9.30). The mutation rate was not associated with the father's age (OR 1.04, 95% CI 0.94-1.15) or the sex of the child (OR 0.95, 95% CI 0.50-1.79). Our results are consistent with both no effect of radiation on minisatellite mutations and a slight increase at dose levels exceeding 20 cSv.     

Congenital Cerebral Palsy,Child Sex and Parent Cardiovascular Risk

Objective

Genes associated with cardiovascular disease may also be risk factors for congenital cerebral palsy (CP) and these associations may be modified by sex, since there is an increased risk of CP in male children. We investigated the association between CP of the child with cardiovascular disease in parents, taking sex of the child into consideration.

Methods

All parents of non-adopted singletons born in Denmark between 1973 and 2003 were included. Parents of a child with CP, confirmed by the Danish National CP registry, were considered exposed. Cox proportional hazards regressions were used to model risk of cardiovascular outcomes for exposed parents compared to all other parents beginning at the child’s 10^th birthday.

Results

We identified 733,730 mothers and 666,652 fathers among whom 1,592 and 1,484, respectively, had a child with CP. The mean age for mothers at end of follow up was 50±8 years. After adjustment for maternal age, parental education, child’s sex, child’s residence, child being small for gestational age and maternal hypertensive disorder during pregnancy, mothers of CP male children had an excess risk of cardiovascular disease (HR: 1.52, 95% CI: 1.16-2.00), attributable mostly to an increased incidence of hypertension and cerebrovascular disease. After additional adjustment for preterm birth, the association was markedly attenuated for cardiovascular disease (1.34, 95%CI: 1.02 - 1.76), became nonsignificant for hypertension, but remained significant for cerebrovascular disease (HR: 2.73, 95% CI: 1.45- 5.12). There was no increased risk of cardiovascular events in mothers of female CP children, or fathers of CP children of any sex.

Conclusions

Women that have a male child with CP are at increased risk for premature cardiovascular disease. Part of this association may be related to risk factors for preterm births.     

Paternal radiation exposure and leukaemia in offspring: the Ontario case-control study.

OBJECTIVES--To test the hypothesis that there is an association between childhood leukaemia and the occupational exposure of fathers to ionising radiation before a child''s conception. DESIGN--Case-control study with eight matched controls per case. SETTING--Regions of Ontario, Canada, with an operating nuclear facility. SUBJECTS--Cases were children (age 0-14) who died from or were diagnosed as having leukaemia from 1950 to 1988 and were born to mothers living in the vicinity of an operating nuclear facility. Controls were identified from birth certificates, matched by date of birth and residence at birth. There were 112 cases and 890 controls. MAIN OUTCOME MEASURES--Paternal radiation exposure was determined by a record linkage to the Canadian National Dose Registry. RESULTS--Six fathers of cases and 53 fathers of controls had had a total whole body dose > 0.0 mSv before the child''s conception, resulting in an odds ratio of 0.87 (95% confidence interval 0.32 to 2.34). There was no evidence of an increased leukaemia risk in relation to any exposure period (lifetime or six months or three months before conception) or exposure type (total whole body dose, external whole body dose, or tritium dose), except for radon exposure to uranium miners, which had a large odds ratio that was not significantly different from the null value. CONCLUSIONS--The findings of this study in Ontario did not support the hypothesis that childhood leukaemia is associated with the occupational exposure of fathers to ionising radiation before the child''s conception.     

Mortality in the Children of Atomic Bomb Survivors and Controls

A continuing study of mortality rates among children born to survivors of the atomic bombings and a suitable group of controls has been updated; the average interval between birth and verification of death or survival is 17 years. The mortality experience is now based on 18,946 children liveborn to parents one or both of whom were proximally exposed, receiving jointly an estimated dose of 117 rem; 16,516 children born to distally exposed parents receiving essentially no radiation; and 17,263 children born to parents not in Hiroshima or Nagasaki at the time of the bombings. No clearly significant effect of parental exposure on child's survival can be demonstrated either by a contingency chi(2) type of analysis or regression analysis. On the basis of the regression data, the minimal gametic doubling dose of radiation of this type for mutations resulting in death during (on the average) the first 17 years of life among liveborn infants conceived 0-13 years after parental exposure is estimated at 46 rem for fathers and 125 rem for mothers. On the basis of experimental data, the gametic doubling dose for chronic, low-level radiation would be expected to be three to four times this value for males and as much as 1000 rem for females.     

Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 1. Evaluation of the cellular composition of peripheral blood and the role of comorbidities in the oppression of hemapoiesis

Residents of the Techa riverside villages chronically exposed to ionizing radiation (the average dose rate in 1951-1956 was 0.047 Gy/year, the maximum reached 2.44 Gy/year) developed marked changes in the cellular composition of peripheral blood. The maximum reduction of peripheral blood counts occurred in the years 1951-1953, after which the beginning of the restoration of cellularity to the control level was observed. The dose rate at this point (1956) was about 0.02 Gy/year. The factors of radiation and non-radiation nature (gender, the age at the onset of exposure, health related disorders) in different combinations affect the number of peripheral blood cells. The influence of dose rate of a chronic radiation exposure on a platelet count takes precedence over other factors. The factors of gender and dose rate determine the number of erythrocytes in exposed persons. The changes accompanying the health status and dose rate significantly affect the number of neutrophils. The influence of comorbidity, age and dose rate on the number of monocytes was noted. A lymphocyte count was mainly determined by the age at the onset of exposure and concomitant diseases. A joint influence of chronic radiation exposure and concomitant diseases increases a mutual action on erythro- and thrombocytopoiesis. The decrease of the dose rate was followed by a gradual predominance of the somatic disease influence on leukocyte (neutrophils, lymphocytes and monocytes) counts.     

Parental age,birth order and tertiary sex ratio in the human population of Punjab,Pakistan

The data of this study, an extension of a previous study on secondary sex ratio in the human population of Muridke, Punjab, Pakistan, are based on the population of Muridke, 27 km north of Lahore, Punjab, Pakistan. Records of deaths of children, at later stages of birth, for different birth ranks, and that of maternal and paternal ages were made. 1000 families were scored for this study. Families providing the required information were included. Data for paternal age and maternal age combination consisted of 4807 total number of children of which 2586 were male. Paternal age and birth order combination was comprised of a total of 4405 children, containing 2316 males. Maternal age and birth order combination consisted of 4658 children, of which 2458 were males. The discrepancy in the number of children in the 3 types of combinations was due to the lack of required information in different groups. Sex ratio based on total number of males in relation to paternal age and maternal age was 0.54. Younger fathers (15-19 years) showed higher sex ratio (0.69). This dropped in paternal age groups 20-24 years (0.59) and 25-29 years (0.51). Younger mothers (15-19 years) showed higher sex ratio (0.62), declines in the age groups 20-24 years (0.52) and 25-29 years (0.51) and rise in age groups 35-39 years (0.55) and 40-44 years (0.54). Chi-square tests were carried out to compare the number of male and female offspring in the paternal age groups 15-19, 20-24, and 25-29 years. These showed highly significant deviation from the expected number. The higher age groups showed nonsignificant differences in the number of male and female offspring. Maternal age groups 15-19, 20-24, and 25-29 years showed highly significant differences in the male and female offspring and nonsignificant results in the higher age groups. Maternal age in relation to paternal age showed positive simple and partial correlations. Sex ratio for the total number of males based on paternal age and birth order was 0.52. 1st birth order showed higher sex ratio (0.55) and decreased in the 2nd (0.50) and 3rd birth orders (0.51), showed increase in the 4th birth order (0.53) and declines in the higher birth ranks. The number of male and female offspring in the birth orders 1, 2, and 3 showed significant differences, but in higher birth ranks the difference was insignificant. Paternal age and birth order indicated positive simple and partial correlations. Higher sex ratio (0.58) was seen in the 1st birth order and then it decreased in the 2nd (0.50) and 3rd (0.51) birth order. Chi-square tests carried out to compare the number of male and female offspring in borth orders 1, 2, and 3 showed highly significant differences but in higher birth ranks the difference was insignificant.     

Glycophorin A somatic cell mutations in a population living in the proximity of the Semipalatinsk nuclear test site

The glycophorin A (GPA) somatic mutation assay was performed to evaluate the magnitude of exposure to ionizing radiation among the human population living in the vicinity of the Semipalatinsk nuclear test site in Kazakhstan. All together, 113 blood samples were analyzed from three generations of people living in villages that were under the trail of the radioactive cloud from the first Soviet surface nuclear test performed in August 1949 and from later tests. The oldest generation (P0) lived in the area at the time of testing, whereas the younger generations (F1, F2) were exposed to smaller doses from the residual fallout and later tests. The GPA assay did not reveal significant differences in the variant cell frequencies for all subjects selected from the Semipalatinsk area compared with 74 matched controls living in a noncontaminated area. However, a significant increase (P < 0.05) in the mean allele-loss ON variant frequency was observed among the exposed P0 generation (12 x 10(-6)) in comparison to controls (7 x 10(-6)). Considering the sensitivity of the GPA assay, the results suggest that the mean dose to the P0 generation of the affected villages was relatively low, a finding which is in accordance to the conclusions obtained from other biological assays performed on the same population.     

Response of the glutathione system to chronic irradiation of human population after the Chernobyl accident

A complex relationship between glutathione level in plasma in human population (children living in radionuclide-contaminated regions and the Chernobyl liquidators) exposed to chronic low-level radiation after the Chernobyl accident was demonstrated. The obtained experimental data indicate different responses of the human glutathione system to low (from 0.1 to 20 cSv) and high (from 20 to 150 cSv) doses of ionizing radiation.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 1, 2005, pp. 9–17.Original Russian Text Copyright © 2005 by Ivanenko, Burlakova.     

The relationship between parental age and birth order with the percentage of low birth-weight infants

Birthweight, birth order, and parental age were abstracted from 1,515,443 New York State birth certificates to study the association between the birth of an infant weighing less than 2501 g and parental age. The percentage of premature infants was greatest for birth order 1 and 6+ and showed a minimum at birth order 3. When maternal age and birth order were analyzed jointly, a strong interaction was found. Young mothers showed a tendency to have an increasing proportion of low birthweight infants with increasing birth order, whereas, the exact opposite was true for mothers older than 45. The intermediate maternal age categories reflected this change from an association of increasing proportion of low birthweight infants with increasing birth order to a pattern of decreasing proportion of premature imfants with increasing birth order. In data stratified to eliminate the influence of maternal age and to some extent birth order, paternal age was shown to affect the percentage of infants weighing less than 2501 g. This association was described by a flat n-shaped curve that was significantly different from a horizontal line (P.01) in 6 of 7 maternal age categories.     

Stable chromosome aberrations in the lymphocytes of a population living in the vicinity of the Semipalatinsk nuclear test site

SalomaTranslocation analysis using FISH (fluorescence in situ hybridization) chromosome painting was performed to evaluate the magnitude of exposure to ionizing radiation among the human population living close to the Semipalatinsk nuclear test site in Kazakhstan. We studied two generations of people living in villages that were in the path of the radioactive cloud from the first Soviet surface nuclear test performed in August 1949 and from later tests. The older generation (P(0)) lived in the area at the time of testing, and the younger generation (F(1)) was exposed to smaller doses from the residual fallout and later tests. In both P(0) and F(1) generations, similar translocation frequencies were observed in persons living in either the Semipalatinsk area or a noncontaminated area. Assuming translocation stability in peripheral blood lymphocytes over several decades, these findings suggest that on average, the magnitude of exposure of this cohort in the Semipalatinsk area has been considerably smaller than that reported in the literature. Previously reported doses of the order of 1-4.5 Gy (mean 2.9 Gy in the P(0) generation) cannot be confirmed by the present data.     

Exogenous sex hormone exposure and the risk for VACTERL association

In several studies investigators have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. A group of malformations, the VACTERL (vertebral, anal, cardiac, trachea, esophageal, renal, limb-acronym) association, has been statistically associated with maternal exposure to exogenous sex hormones during the first trimester of pregnancy. The VACTERL association is a nonrandom group of major malformations that occur together more often than would be expected on the basis of chance. To assess this association, we conducted a case-control study of first-trimester exposure to sex hormones among mothers of 34 infants with the VACTERL association and of 1,024 comparison infants with one or more of ten major malformations or Down syndrome. The study subjects were malformed infants born between July 1970 and June 1979 and registered in a population-based birth defects registry. Information concerning the use of exogenous sex hormones during pregnancy was obtained by systematically interviewing the mothers of the malformed infants. Most of the mothers were interviewed within 6 months of their children's births. Each mother was interviewed within a year of her child's birth. We found an odds ratio of 0.98 (90% confidence limits 0.40, 2.38) for the relationship between VACTERL association and use of any sex hormone in the first trimester of pregnancy. Our study had adequate statistical power to detect a true relative risk of 2.8 or greater.     

Paternal effects on the human sex ratio at birth: evidence from interracial crosses

The effects of interracial crossing on the human sex ratio at birth were investigated using United States birth-certificate data for 1972-1979. The sex ratio was 1.059 for approximately 14 million singleton infants born to white couples, 1.033 for 2 million born to black couples, and 1.024 for 64,000 born to American Indian couples. Paternal and maternal race influences on the observed racial differences in sex ratio were analyzed using additional data on approximately 97,000 singleton infants born to white-black couples and 60,000 born to white-Indian couples. After adjustment for mother's race, white fathers had significantly more male offspring than did black fathers (ratio of sex ratios [RSR] = 1.027) and Indian fathers (RSR = 1.022). On the other hand, after adjustment for father's race, white mothers did not have more male offspring than did black mothers (RSR = 0.998) or Indian mothers (RSR = 1.009). The paternal-race effect persisted after adjustment for parental ages, education, birth order, and maternal marital status. The study shows that the observed racial differences in the sex ratio at birth are due to the effects of father's race and not the mother's. The study points to paternal determinants of the human sex ratio at fertilization and/or of the prenatal differential sex survival.