Cancer Risks in Parents Who had a Child with a Congenital Malformation

Cancer risk in parents may be related to congenital malformations (CMs) in their children if they share genetic susceptibility or environmental exposure that may be teratogenic and carcinogenic. We conducted a population‐based cohort study based on Danish register data. We identified 795,607 mothers and 781,424 fathers who had all their children between 1977 and 2007 in Denmark. Information on CM was obtained from the Danish Hospital Registry and information on cancer was obtained from the Danish Cancer Registry. Parents were followed from the birth of their first child until the diagnosis of cancer, death, emigration, or December 31, 2007. We used Cox regression models to estimate hazard ratios (HRs) for cancer including cancer in specific organs in mothers and fathers. Overall, 75,701 (9.5%) mothers and 72,724 (9.3%) fathers had at least one child diagnosed with CMs within the first year of life. Neither mothers (HR = 1.04; 95% CI: 0.99–1.04) nor fathers (HR = 1.03; 95% CI: 0.98–1.09) who had a child with a CM had a higher overall risk of cancer. Mothers (HR = 0.76, 95% CI: 0.58–1.00) or fathers (HR = 0.89, 95% CI: 0.66–1.19) who had a child with a chromosomal malformation had a lower overall cancer risk. The findings also showed a higher risk for some specific types of cancer in parents who had children with a CM in the specific system. Some, or perhaps all, of these findings may be due to chance caused by multiple comparisons. We present all results on paper or online to provide clues for further research and to avoid publication bias.     

Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria.

OBJECTIVE--To examine whether the observed excess of childhood leukaemia and lymphoma near the Sellafield nuclear plant is associated with established risk factors or with factors related to the plant. DESIGN--A case-control study. SETTING--West Cumbria health district. SUBJECTS--52 Cases of leukaemia, 22 of non-Hodgkin''s lymphoma, and 23 of Hodgkin''s disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25 and 1001 controls matched for sex and date of birth taken from the same birth registers as the cases. MAIN OUTCOME MEASURES--Antenatal abdominal x ray examinations, viral infections, habit factors, proximity to and employment characteristics of parents at Sellafield. RESULTS--Expected associations with prenatal exposure to x rays were found, but little information was available on viral illnesses. Relative risks for leukaemia and non-Hodgkin''s lymphoma were higher in children born near Sellafield and in children of fathers employed at the plant, particularly those with high radiation dose recordings before their child''s conception. For example, the relative risks compared with area controls were 0.17 (95% confidence interval 0.05 to 0.53) for being born further than 5 km from Sellafield 2.44 (1.04 to 5.71) for children of fathers employed at Sellafield at their conception, and 6.42 (1.57 to 26.3) for children of fathers receiving a total preconceptual ionising radiation dose of 100 mSv or more. Other factors, including exposure to x rays, maternal age, employment elsewhere, eating seafood, and playing on the beach did not explain these relationships. Focusing on Seascale, where the excess incidence has predominantly been reported, showed for the four out of five cases of leukaemia and one case of non-Hodgkin''s lymphoma whose fathers were employed at Sellafield and for whom dose information was obtained that the fathers of each case had higher radiation doses before their child''s conception than all their matched control fathers; the father of the other Seascale case (non-Hodgkin''s lymphoma) was not employed at the plant. These results seem to explain statistically the geographical association. For Hodgkin''s disease neither geographical nor employment associations with Sellafield were found. CONCLUSIONS--The raised incidence of leukaemia, particularly, and non-Hodgkin''s lymphoma among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception. The association can explain statistically the observed geographical excess. This result suggests an effect of ionising radiation on fathers that may be leukaemogenic in their offspring, though other, less likely, explanations are possible. There are important potential implications for radiobiology and for protection of radiation workers and their children.     

Parental consanguinity as a cause for increased incidence of births defects in a study of 238,942 consecutive births.

The risk for birth defects in the offspring of first-cousin matings has been estimated to increase sharply compared to non consanguineous marriages. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies we tried to answer to this question. In the population studied in North-Eastern France a consanguineous mating was known in 1.21% of the cases with congenital anomalies, vs. 0.27% in controls, (p < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 89 malformed children, 51 were seen in first-cousins mating (10.3 times more frequent than in offspring of non consanguineous couples), 17 in second-cousins marriages and 18 in more distant relatives mating. Three were uncle-niece marriage. Excluding known mendelian conditions these numbers were 73, 36, 17 and 17 respectively and the corresponding relative risk were 3.68, 3.01, 3.41 and 4.89 respectively. Therefore there is a negative dose-response effect between level of inbreeding and risk of congenital malformations. Consanguineous mothers were more often pregnant than non consanguineous mothers (p < 0.01) and they had more stillbirths than non consanguineous mothers. These results show that consanguinity is still a factor of birth defects and they must be taken into account for genetic counseling of inbred marriages, in developed countries.     

Dermatoglyphic studies in the parents of trisomy 21 children I. Distribution of dermatoglyphic discriminants

A sample of 312 parents of a child with complete trisomy 21 (168 mothers and 144 fathers) has been compared with 295 parents of non-mongol children (61 mothers and 134 fathers) with respect to distribution of individual dermatoglyphic discriminant scores. Selection of dermatoglyphic traits as well a weightings have been based on the discriminant function, constructed for normal controls against cytogenetically diagnosed trisomy 21 mosaics. The results indicate that the proportion of individuals with an increased chance of mosaicism is appreciably greater in a sample of both the mothers and the fathers of mongol children, as compared with the parents of non-mongol children. For D greater than + 3.00, including also the overlap range values, it is, on the average, twice as high as in the control parents, while for the D values greater than + 4.00, strongly indicative of mosaicism, it is about five times higher than in control parents. This is so in spite of the fact that all parents, who had previously been cytogenetically tested and diagnosed as mosaics, were not included in this sample. Although the meaning of these results cannot yet be completely understood, they justify the extension of the use of dermatoglyphic discriminants in studies on parental mosaicism in trisomy 21.     

Self-reported reading problems in parents of twins with reading difficulties.

Parents of 323 twin pairs with reading disability (RD) reported significantly more problems learning to read (16% of mothers and 33% of fathers) than parents of 309 twin pairs without reading difficulties (6% of mothers and 9% of fathers). These rates of self-reported reading problems in parents of twins are highly similar to those previously obtained in parents of non-twin children with RD and controls, suggesting that the etiology of reading deficits in twin and non-twin children may also be highly similar. Moreover, within both the RD and control samples, twins whose parents self-reported a positive history of reading problems had lower reading performance test scores, on average, than those whose parents reported no reading problems. Therefore, results of the present twin study support those of previous studies with non-twin children in which parental self-reports have been found to provide a valid index of family history status for reading difficulties.     

Children killed by genetic parents versus stepparents

Despite many empirical studies of children killed by parents, there has been little theoretical progress. An examination of 378 cases in a national register revealed that circumstances differed for genetic parents versus stepparents. Infants were at greatest risk of filicide, especially by genetic mothers. Genetic mothers who killed offspring, especially older children, disproportionately had a mental illness and received relatively short sentences, if convicted. Filicides by genetic fathers were disproportionately accompanied by marital discord, suicide, and uxoricide. Filicides by stepparents were disproportionately common and likely to involve ongoing abuse and death by beating. Moreover, if parents also had genetic offspring, their stepchildren were at increased risk of ongoing abuse and neglect prior to death. Poor child health appeared to increase the risk of filicide by genetic mothers, especially as remaining opportunities for childbearing diminished. Although each finding might be consistent with existing lay accounts of filicide (depression, socioeconomic stress, etc.), together, they yielded a pattern uniquely consistent with selectionist accounts based mainly on parental investment theory.     

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.     

Higher risk of seizures in offspring of mothers than of fathers with epilepsy.

Seizure risk has consistently been found to be higher in offspring of mothers than of fathers with epilepsy. This pattern cannot be explained by any simple genetic model. The present study examined the possibility that the pattern arises from differences between affected mothers and fathers in the characteristics of their epilepsy that influence offspring seizure risk. The study population comprised 687 offspring of parents with epilepsy from the Rochester-Olmsted County Record Linkage Project. Cumulative incidences of unprovoked seizures to age 25 were 8.7% and 2.4% in offspring of affected mothers and fathers, respectively. Cox proportional hazards analysis was used to calculate rate ratios (RRs) for unprovoked seizures in offspring. In the univariate analysis, risk of unprovoked seizures was higher if the affected parent was the mother (RR = 2.8, 95% confidence interval [ci] 1.1-7.2) or if the parent's onset was before age 20 (RR = 2.5, 95% ci 1.1-5.9), but there was no effect on offspring risk of either parent's etiology (idiopathic vs. remote symptomatic) or parent's seizure type (generalized vs. partial). These findings were not substantially changed in the multivariate analysis. Thus, differences between affected mothers and fathers in these characteristics did not account for the higher risk in offspring of affected mothers. Anticonvulsant use during pregnancy was not associated with increased offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Offspring of male and female parents with thalidomide embryopathy: birth defects and functional anomalies

BACKGROUND: The aim of the study was to evaluate congenital malformations and functional anomalies in the offspring of Swedish parents with thalidomide embryopathy (TE). METHODS: Sixty-four children (29 girls, 35 boys) with ages ranging from 0-18 years, born to 34 Swedish parents (14 women, 20 men) with TE, were studied. Data on malformations and dysfunction were collected from medical records at maternity and child healthcare units, delivery units, hospitals, outpatient clinics and schools. RESULTS: Five children had both a mother and father with TE, 23 had a mother suffering from TE, and in 36 children the father had TE. One girl had a major malformation consisting of pulmonary stenosis, and single cases of minor physical features and positional deformities were observed. One boy had autism. Four children were born preterm, all to a TE mother. One child died within 24 hr after birth. Seven spontaneous abortions were registered, five of them in TE mothers. The cesarian section rate was 39% among the TE mothers, compared to 14% among the non-TE mothers. CONCLUSIONS: Malformations or functional anomalies similar to those typical for TE were not found in this group of children born to Swedish parents with TE. Cesarian sections were more frequently performed in TE mothers, partly because of pelvic and uterine malformations.     

Sociodemographic and motivational characteristics of parents who volunteer their children for clinical research: a controlled study.

OBJECTIVE--To determine the sociodemographic and motivational characteristics of parents who volunteer their children for clinical research. DESIGN--A questionnaire was administered to parents who volunteered their children for a randomised, double blind, placebo controlled trial of a drug to treat asthma and to a control group of parents whose children were eligible for the trial but had refused the invitation. SETTING--A children''s hospital in Australia. SUBJECTS--68 Parents who had volunteered their children and 42 who had not; a response rate of 94% and 70%, respectively. MAIN OUTCOME MEASURES--Responses of parents to questionnaire designed to assess their perceptions, attitudes, and health seeking behaviour as well as sociodemographic data. RESULTS--Volunteering parents were less well educated with only 15% (10/68) of mothers and 16% (11/68) and of fathers having had a tertiary or university education compared with 26% (11/42) of mothers and 45% (19/42) in the non-volunteering group. Fewer volunteering parents had professional or administrative jobs than did non-volunteering parents (mothers 6% (4/68); fathers 9% (6/68) v mothers 14% (6/42); fathers 31% (13/42)). Volunteering parents had less social support, and they displayed greater health seeking behaviour and consumed more habit forming substances. They were motivated by a desire to help others and to contribute to medical research, but they were also searching for more information and better ways to help their own children. CONCLUSION--Parents who volunteer their children for medical research are significantly more socially disadvantaged and emotionally vulnerable.     

Case-control study of leukaemia and non-Hodgkin's lymphoma among children aged 0-4 years living in west Berkshire and north Hampshire health districts.

OBJECTIVE--To investigate the relation between parental employment in the nuclear industry and childhood leukaemia and non-Hodgkin''s lymphoma. DESIGN--Case-control study. SETTING-West Berkshire and Basingstoke and North Hampshire District Health Authorities. SUBJECTS--54 children aged 0-4 years who had leukaemia or non-Hodgkin''s lymphoma diagnosed during 1972-89, who were born in the study area and were resident there when cancer was diagnosed. Six controls were selected for each case: four from hospital delivery registers and two from livebirth registers maintained by the NHS central register. Controls were matched for sex, date of birth (within six months), and area of residence at birth and time of diagnosis. MAIN OUTCOME MEASURES--Parents'' employment by the nuclear industry and exposure to ionising radiation at work. RESULTS--Five (9%) of the 54 cases and 14 (4%) of the 324 controls had fathers or mothers, or both, who had been employed by the nuclear industry (relative risk 2.2, 95% confidence interval 0.6 to 6.9). Nuclear industry employees who work in areas where exposure to radiation is possible are given film badges to monitor their exposure to external penetrating ionising radiation. Three fathers of cases and two fathers of controls (and no mothers of either) had been monitored in this way before their child was conceived (relative risk 9.0, 95% confidence interval 1.0 to 107.8). No father (of a case or control) had accumulated a recorded dose of more than 5 mSv before his child was conceived, and no father had been monitored at any time in the four years before his child was conceived. A dose-response relation was not evident among fathers who had been monitored. CONCLUSIONS--These results suggest that the children of fathers who had been monitored for exposure to external penetrating ionising radiation in the nuclear industry may be at increased risk of developing leukaemia before their fifth birthday. The finding is based on small numbers and could be due to chance. If the relationship is real the mechanisms are far from clear, except that the effect is unlikely to be due to external radiation; the possibility that it could be due to internal contamination by radioactive substances or some other exposure at work should be pursued. The above average rates of leukaemia in the study area cannot be accounted for by these findings.     

Risk for congenital anomalies associated with different sporadic and daily doses of alcohol consumption during pregnancy: a case-control study

BACKGROUND: The classic clinical criteria for the diagnosis of fetal alcohol syndrome (FAS) include a "characteristic" facial appearance, pre- and postnatal growth deficiency, microcephaly, mental retardation, and occasional major malformations. However, diagnostic constraints, especially in the newborn period, lead to an underestimate of their prevalence. We report an epidemiological study of the potential risk of congenital defects in the offspring of mothers who ingested different sporadic and daily amounts of alcohol during pregnancy. METHODS: The study was based on the data from the ECEMC hospital-based case-control study and surveillance system, with a methodology aimed not only at the surveillance of congenital anomalies, but also at investigating their characteristics, clustering, and causes. For the purposes of this study, we considered as exposed those infants whose mothers reported the ingestion of any amount of alcohol during gestation (4705 mothers of cases and 4329 mothers of controls), and classified them into five groups according to their levels of alcohol consumption. Two groups consisted of mothers who consumed increasing sporadic levels and the other three consisted of mothers who consumed increasing daily levels of alcohol. RESULTS: Our study showed that even low sporadic doses of alcohol consumption during pregnancy may increase the risk of congenital anomalies in the offspring and that this risk increases with increasing levels of alcohol exposure. CONCLUSIONS: The results of our study suggest that it is necessary to generalize the preventive norm and recommend complete abstinence from alcohol during gestation. Birth Defects Research (Part A), 2004.     

Association between childhood atopic disease and parental atopic disease in a population with high consanguinity

The aim of the study was to investigate the association between asthma, allergic rhinitis, and eczema in Qatari schoolchildren with allergic conditions in their parents. A cross-sectional study was conducted among 3500 Qatari schoolchildren aged 6-14 years in period: February, 2003-February, 2004. A questionnaire was used to collect the clinical history of asthma and allergic rhinitis in their parents and siblings. It was found that 21.6% of asthmatic children had mothers with asthma and 18.2% fathers with asthma. This contrasted with 6.8% of non-asthmatic children who had fathers with asthma and 9.4% mothers with asthma. As for allergic rhinitis, 26.5% of asthmatic children had mothers with allergic rhinitis and 25.3% fathers with allergic rhinitis. The frequency of either parent of the asthmatic children having allergic rhinitis was 41.8% and for both parents was 10.0%. The frequency of siblings having asthma was 36.6%, allergic rhinitis 16.4%, and eczema 29.1%. The present study revealed a strong association between respiratory allergies and eczema in parents, and their asthmatic children.     

What happens to offspring when parents are inbred,old or had a poor start in life? Evidence for sex‐specific parental effects

Parental effects on offspring performance have been attributed to many factors such as parental age, size and condition. However, we know little about how these different parental characteristics interact to determine parental effects, or the extent to which their effect on offspring depends on either the sex of the parent or that of the offspring. Here we experimentally tested for effects of variation in parents’ early diet and inbreeding levels, as well as effects of parental age, and for potential interactive effects of these three factors on key aspects of offspring development in the mosquitofish (Gambusia holbrooki). Older mothers produced offspring that were significantly smaller at birth. This negative effect of maternal age on offspring size was still evident at maturation as older mothers had smaller daughters, but not smaller sons. The daughters of older mothers did, however, reach maturity sooner. Paternal age did not affect offspring body size, but it had a complex effect on their sons’ relative genital size. When initially raised on a food‐restricted diet, older fathers sired sons with relatively smaller genitalia, but when fathers were initially raised on a control diet their sons had relatively larger genitalia. The inbreeding status of mothers and fathers had no significant effects on any of the measured offspring traits. Our results indicate that the manifestation of parental effects can be complex. It can vary with both parent and offspring sex; can change over an offspring's life; and is sometimes evident as an interaction between different parental traits. Understanding this complexity will be important to predict the role of parental effects in adaptation.     

The use of dysmorphology in birth defects epidemiology.

Most human teratogens have been identified by the clinical recognition of characteristic patterns of congenital anomalies among children whose mothers were exposed to a particular agent during pregnancy. Although this dysmorphologic method has been valuable, it is criticized because it is not easily amenable to statistical evaluation. Conventional birth defects epidemiological studies are designed to permit rigorous statistical assessment, but such investigations usually classify congenital anomalies without adequate consideration of their known etiological heterogeneity. It is possible to combine the best aspects of these two approaches to identifying human teratogens in a "dysmorphologic case/control study." Instead of including all available cases with a given defect, only individuals having the anomaly in the context of a multiple congenital anomaly pattern without a recognizable cause would be selected for inclusion among the case group. The frequency of exposure to the putative teratogen would be determined among these selected cases and among appropriately chosen controls; conventional statistical analysis would then be performed. Although this design reduces the size of the case group compared to a conventional case/control study, the statistical power is unchanged or increased. In addition, biological plausibility is increased by concentrating upon a group of cases that is more likely to have a teratogenic cause.     

Employment Situation of Parents of Long-Term Childhood Cancer Survivors

Background

Taking care of children diagnosed with cancer affects parents’ professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment.

Methods

As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5–15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5–15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry.

Results

We included 394 parent-couples of survivors and 3’341 control parents (1’731 mothers; 1’610 fathers). Mothers of survivors were more often not employed (29% versus 22%; p_trend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; p_trend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14–5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71–7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13–0.73) and >2 children (OR = 0.48, CI:0.30–0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04–0.36).

Conclusion

Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.     

A Preliminary Investigation of Parent–Progeny Olfactory Recognition and Parental Investment

The role of olfaction in kin recognition and parental investment is documented in many mammalian/vertebrate species. Research on humans, however, has only focused on whether parents are able to recognize their children by smell, not whether humans use these cues for investment decisions. Here we show that fathers exhibit more affection and attachment and fewer ignoring behaviors toward children whose smell they can identify than toward those whose smell they cannot recognize. Thus, olfaction might serve as a means for males to determine their genetic relatedness to purported offspring. We also demonstrate that mothers’ olfactory recognition and hedonistic ratings are linked with the use of physical punishment. Mothers report using more punishment with children whose odor they cannot recognize and less with children whose odor they rated as more pleasant. These results provide the first preliminary evidence in humans that olfactory cues may guide parents in the allocation of care.     

Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk

Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range. In three cohorts (cohort 1: n = 1,988, aged 0–18 years; cohort 2: n = 300, 8–30 years; cohort 3: n = 369, 18–60 years), we measured lipid and lipoproteins as well as carotid intima-media thickness (c-IMT) in offspring from FH mothers versus FH fathers. For LDL cholesterol, triglycerides (TGs), and c-IMT, we performed a pooled analysis. No significant differences could be observed in c-IMT, lipid, or lipoprotein levels from offspring of FH mothers versus FH fathers. Pooled analyses showed no significant differences for either LDL cholesterol [mean difference 0.02 (−0.06,0.11) mmol/l, P = 0.60], TGs [mean difference 0.07 (0.00,0.14) mmol/l, P = 0.08], or c-IMT [mean difference −0.00 (−0.01,0.01) mm, P = 0.86]. Our data do not support the hypothesis that cardiovascular risk markers are different between offspring from FH mothers and FH fathers.     

Paternal preconceptional radiation exposure in the nuclear industry and leukaemia and non-Hodgkin's lymphoma in young people in Scotland.

OBJECTIVE--To determine if a relation exists between paternal exposure to relatively high levels of radiation in the Scottish nuclear industry and the risk of leukaemia and non-Hodgkin''s lymphoma is subsequently conceived children. DESIGN--Matched case-control study with three controls for each case. SETTING--The whole of Scotland. SUBJECTS--The fathers of 1024 children with leukaemia and 237 children with non-Hodgkin''s lymphoma diagnosed in Scotland below the age of 25 among those born in Scotland since nuclear operations began (in 1958) and the fathers of 3783 randomly chosen controls. The fathers of 80 children with leukaemia and 16 with non-Hodgkin''s lymphoma in north Cumbria were also covered since some workers at one Scottish nuclear site live over the border in that area. Details of all fathers were then matched against records of the nuclear industry. MAIN OUTCOME MEASURES--Paternal preconceptional radiation exposures, particularly relatively high levels, both lifetime and in the six and three months before conception. RESULTS--No significant excess was observed in any subgroup and there was no significant trend: fathers of three controls but no cases were exposed to lifetime preconceptional levels of 100 mSv or greater (Fisher''s exact p value 0.84). In the six months before conception, fathers of two cases and three controls received 10 mSv or more, odds ratio 2.3 (95% confidence interval 0.31 to 17.24). In the three months before conception the fathers of one case and two controls received 5 mSv or more, odds ratio 1.7 (0.10 to 30.76). The results for leukaemia and non-Hodgkin''s lymphoma combined were similar. CONCLUSIONS--No significant excess of leukaemia or of leukaemia and non-Hodgkin''s lymphoma was found at any radiation level in any preconceptional period.