Diagnostic X-rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia by immunophenotype.

The objective of this study was to evaluate the association between in utero diagnostic X-rays and childhood acute lymphoblastic leukemia (ALL) and the less well-studied relationship of this malignancy to preconception and postnatal diagnostic X-rays or fetal ultrasound exposures. The Children's Cancer Group conducted a case-control study including interviews with parents of 1842 ALL cases diagnosed under the age of 15 years and 1986 individually matched controls. Associations of self-reported parental preconception, in utero, and postnatal X-ray exposure with risk of childhood ALL were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs) obtained from logistic regression models among the overall group of ALL cases as well as immunophenotypic and age-specific subgroups. Overall, in utero pelvimetric diagnostic X-rays were not associated with the risk of pediatric ALL (OR, 1.2; 95% CI, 0.8-1.7). Childhood ALL, all types combined (OR, 1.1; 95% CI, 0.9-1.2) and specific types were also not linked with postnatal diagnostic X-ray exposures. Neither maternal (OR, 0.9; 95% CI, 0.8-1.2) nor paternal (OR, 1.1; 95% CI, 0.8-1.4) lower abdominal preconception diagnostic X-rays were associated with risk of childhood ALL. Among the multiple comparisons for age-, sex-, and subtype-specific subgroups, we observed an elevated risk of total ALL among children ages 11-14 at diagnosis (OR, 2.4; 95% CI, 1.1-5.0) in relation to in utero pelvimetric diagnostic X-ray exposures and a small increase in pre-B ALL for all ages combined (OR, 1.7; 95% CI, 1.1-2.7) in relation to postnatal diagnostic X-rays. In utero diagnostic ultrasound tests were not linked with risk of childhood ALL. We found little consistent evidence that in utero diagnostic ultrasound tests or X-rays were linked with an increased risk of childhood ALL. Small increases in total or pre-B ALL risks for children in selected age groups to very low ionizing radiation exposures from postnatal or preconception diagnostic X-ray exposures may represent chance findings or biases. Future studies of diagnostic X-rays and childhood leukemia in the United States will require extensive additional efforts and resources to quantify risk because of declining in utero exposures in the general population (thus necessitating large numbers of subjects, particularly cases) and the difficulty in validating reported exposures.     

Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany.

In order to investigate the associations between sources of exposure to ionizing radiation and childhood cancer in Germany, a matched case-control study including children under the age of 15 years was conducted. Cases were identified from the German Childhood Cancer Registry; controls came from population registration offices. Exposure was assessed via questionnaires and parental interviews. The study comprises 1184 leukemia cases, 234 non-Hodgkin's lymphomas, 940 solid tumors, and 2588 controls. Preconception parental occupational exposures were positively but not statistically significantly related to all of the cancer types in the study. Maternal occupational exposure during pregnancy was a risk factor for childhood lymphomas [odds ratio (OR) = 3.87, 95% confidence interval (CI): 1.54-9.75] but not for leukemia or solid tumors. ORs for parental occupational exposures were noticeably more pronounced in leukemia cases who were diagnosed in their first 18 months of life. A preconception paternal occupation in the nuclear industry under dosimetric surveillance yielded an OR of 1.80 (95% CI: 0.71-4.58). However, radiation doses of these fathers were often unknown or below the level of detection, and no dose exceeded 30 mSv. Prenatal X-ray examinations of the father (but not of the mother) were significantly related to childhood leukemia (OR = 1.33; 95% CI: 1.10-1.61). No effects were observed for postnatal X-ray examinations of the child. The results suggest that, in Germany at present, exposures to ionizing radiation do not play a noticeable role in the development of childhood cancers. The major strengths of the study are its size and the population basis. The validity of the data from parental questionnaires and the possibility of residual confounding by socioeconomic factors are potential drawbacks.     

Prenatal X-ray exposure and childhood cancer in Swedish twins

The association between X-ray exposure in utero and childhood cancer was studied in a case-control study, nested in a national cohort of Swedish twin births. Records of the Swedish Twin Register for those born 1936-1967 (n = 83,316) were linked to the Swedish Cancer Register (1958-1983) and the Swedish Cause-of-Death Register (1952-1983). Ninety-five cases of childhood cancer before the age of 16 were identified. Two controls from the Twin Register were matched to each case by sex and year of birth. Maternal X-rays during pregnancy were documented for 41% of the cases and 36% of the controls. The crude relative risk of any childhood cancer associated with any prenatal X-ray was 1.2 (95% CI; 0.7-2.1). For the cases 64% of the X-rayed women had had abdominal X-rays, the numbers for the controls were 57%. Fifty-nine per cent of the X-rayed women had had abdominal X-rays, which were associated with a relative risk for all cancers of 1.4 (Cl; 0.8-2.5), leukemias 1.7 (Cl; 0.7-4.1) and tumors of the central nervous system 1.5 (Cl; 0.5-4.2). There was no apparent confounding by mother's age, drug use, obstetric complications, previous miscarriages, social class or length of pregnancy. The observed relative risks of cancer following prenatal X-ray exposure are consistent with previous studies, suggesting that the developing fetus may be more sensitive to the carcinogenic effects of ionizing radiation than are children irradiated post-natally.     

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.     

Cancer in the offspring of female radiation workers: a record linkage study

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child''s conception may be at an increased risk of childhood cancer. An additional 16 964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52 612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.     

Risk of childhood leukemia and parental self-reported occupational exposure to chemicals, dusts, and fumes: results from pooled analyses of German population-based case-control studies.

A recent large-scale United States study reported an association between parental exposure to hydrocarbons at work and the risk of childhood leukemia. Parental occupational exposure to different chemicals and industrial dusts or fumes also was assessed in three German case-control studies that were conducted from 1992-1997. The design and methods of exposure assessment were similar for these studies; therefore, they were pooled for this analysis. In total, these three studies involved 1138 cases of acute lymphocytic leukemia (ALL) and 2962 controls. We found that maternal exposure to paints or lacquers during the preconception period (odds ratio, 1.6; 95% confidence interval, 1.1-2.4) and during the index pregnancy (odds ratio, 2.0; 95% confidence interval, 1.2-3.3) was related to an increased risk of childhood ALL. Whereas our findings for exposure to paints or lacquers confirmed observations from the United States study, we failed to confirm associations between risk of ALL and maternal exposure to solvents and parental exposure to plastic materials. Our studies provide some evidence that parental occupational exposure to certain substances may be associated with cancer risk in offspring; however, more specific studies are needed to identify such substances and the doses that may be hazardous.     

Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring.

Parental exposure to hydrocarbons at work has been suggested to increase the risk of childhood leukemia. Evidence, however, is not entirely consistent. Very few studies have evaluated the potential parental occupational hazards by exposure time windows. The Children's Cancer Group recently completed a large-scale case-control study involving 1842 acute lymphocytic leukemia (ALL) cases and 1986 matched controls. The study examined the association of self-reported occupational exposure to various hydrocarbons among parents with risk of childhood ALL by exposure time window, immunophenotype of ALL, and age at diagnosis. We found that maternal exposure to solvents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.3-2.5] and paints or thinners (OR, 1.6; 95% CI, 1.2-2.2) during the preconception period (OR, 1.6; 95% CI, 1.1-2.3) and during pregnancy (OR, 1.7; 95% CI, 1.2-2.3) and to plastic materials during the postnatal period (OR, 2.2; 95% CI, 1.0-4.7) were related to an increased risk of childhood ALL. A positive association between ALL and paternal exposure to plastic materials during the preconception period was also found (OR, 1.4; 95% CI, 1.0-1.9). The ALL risk associated with parental exposures to hydrocarbons did not vary greatly with immunophenotype of ALL. These results suggest that the effect of parental occupational exposure to hydrocarbons on offspring may depend on the type of hydrocarbon and the timing of the exposure.     

Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia

Diagnostic X-ray examinations as a potential risk for neoplasia were investigated in a prospective study of 55,908 women who participated in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. The X-ray exposure histories of 145 mothers whose children developed neoplasms and 290 matched controls were examined. Of the childhood neoplasms, 40 were malignant and 105 were benign. Generally, the data were consistent with increased risk of malignant neoplasms among children of women exposed to X-rays before and during pregnancy, with a somewhat higher relative risk estimate for preconception exposure. No significant association of X-ray exposure and benign neoplasms was detected.     

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case - control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers.     

Prenatal ultrasound and the risk of childhood brain tumour and its subtypes

We carried out a nationwide case-control study of childhood brain tumours in Sweden (n=512) by histological subtype in relation to prenatal ultrasound, extracting data from antenatal records and the Medical Birth Register. We found no increased risk for brain tumour after ultrasound exposure, either for all tumours or for any subgroup.     

Prenatal X-ray exposure and childhood brain tumours: a population-based case-control study on tumour subtypes

We investigated childhood brain tumours by histological subtype in relation to prenatal X-ray among all children, less than 15 years of age, born in Sweden between 1975 and 1984. For each case, one control was randomly selected from the Medical Birth Register, and exposure data on prenatal X-ray were extracted blindly from antenatal medical records. Additional information on maternal reproductive history was obtained from the Medical Birth Register. We found no overall increased risk for childhood brain tumour after prenatal abdominal X-ray exposure (adjusted odds ratio (OR): 1.02, 95% confidence interval (CI): 0.64-1.62); primitive neuroectodermal tumours had the highest risk estimate (OR: 1.88, 95% CI: 0.92-3.83).     

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose externalradiation over their working lifetime, and they may under risk of different cancers. This study aims to determinethe relationship between the occupational X-ray radiation exposure and cancer risk among these workers inJiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposureand cancer risk. Data were collected through self-administered questionnaire, which includes but not limitsto demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction wasconducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests wereused to compare the differences between each group. We used the logistic regression model to calculate the oddsratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer casesand 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2).Our study found that the occupational radiation exposure was associated with a significantly increased cancerrisk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI:1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancerrisk, which indicates that proper intervention and prevention strategies may be needed in order to bring downthe occupational cancer risk.     

Childhood cancer and residential proximity to power lines. UK Childhood Cancer Study Investigators

In the United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of England, Scotland and Wales, measured power-frequency magnetic fields were not found to be associated with risk for any malignancy. To examine further the risk associated with residential proximity to electricity supply equipment, distances to high-voltage lines, underground cables, substations and distribution circuits were collected for 3380 cases and 3390 controls. Magnetic field exposure from this equipment was calculated using distance, load and other circuit information. There was no evidence that either proximity to electrical installations or the magnetic field levels they produce in the UK is associated with increased risk of childhood leukaemia or any other cancer. Odds ratios of 0.73 (95% CI = 0.42-1.26) for acute lymphoblastic leukaemia, 0.75 (95% CI = 0.45-1.25) for all leukaemias, 1.08 (95% CI = 0.56-2.09) for central nervous system cancers and 0.92 (95% CI = 0.64-1.34) for all malignancies were obtained for residence within 50 m of an overhead line. When individuals with a calculated magnetic field exposure > or = 0.2 microT were compared to those in a reference category of exposure <0.1 microT, odds ratios of 0.51 (95% CI = 0.11-2.33) for acute lymphoblastic leukaemia, 0.41 (95% CI = 0. 09-1.87) for total leukaemia, 0.48 (95% CI =0.06-3.76) for central nervous system cancers and 0.62 (95% CI = 0.24-1.61) for all malignancies were obtained.     

ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis

Radiotherapy is associated with a risk of subsequent neoplasms (SN) in childhood cancer survivors. It has been shown that children’s thyroid glands are especially susceptible. The aim is to quantify the risk of a second neck neoplasm after primary cancer radiotherapy with emphasis on thyroid cancer. We performed a nested case–control study: 29 individuals, diagnosed with a solid SN in the neck region, including 17 with thyroid cancer, in 1980–2002 and 57 matched controls with single neoplasms were selected from the database of the German Childhood Cancer Registry. We investigated the risk associated with radiotherapy exposure given per body region, adjusted for chemotherapy. 16/17 (94.1 %) thyroid SN cases, 9/12 (75 %) other neck SN cases and 34/57 (59.6 %) controls received radiotherapy, with median doses of 27.8, 25 and 24 Gy, respectively. Radiotherapy exposure to the neck region increased the risk of the other neck SNs by 4.2 % (OR = 1.042/Gy (95 %-CI 0.980-1.109)) and of thyroid SN by 5.1 % (OR = 1.051/Gy (95 %-CI 0.984-1.123)), and radiotherapy to the neck or spine region increased the thyroid risk by 6.6 % (OR = 1.066/Gy (95 %-CI 1.010-1.125)). Chemotherapy was not a confounder. Exposure to other body regions was not associated with increased risk. Radiotherapy in the neck or spine region increases the risk of thyroid cancer, while neck exposure increases the risk of any other solid SN to a similar extent. Other studies showed a decreasing risk of subsequent thyroid cancer for very high doses; we cannot confirm this.     

Cohort study of diet, lifestyle, and prostate cancer in Adventist men

Dietary and lifestyle characteristics were evaluated in relation to subsequent prostatic cancer risk in a cohort of approximately 14,000 Seventh-day Adventist men who completed a detailed lifestyle questionnaire in 1976 and who were monitored for cancer incidence until the end of 1982. During the 6-year follow-up period, 180 histologically confirmed prostatic cancers were detected among some 78,000 man-years of follow-up. Increasing educational attainment was associated with significantly decreased risk of prostate cancer in this study; age at first marriage was also inversely associated with risk, although this was not significant. There was no relationship between body mass index (as measured by Quetelet's Index) and risk. A history of prostate "trouble" was associated with a 60% increase in risk which was highly significant. Although there were suggestive relationships between increasing animal product consumption and increased risk, these results did not persist after accounting for the influence of fruit and vegetable consumption. Nor was exposure to the vegetarian lifestyle during the childhood years associated with alterations in subsequent risk. However, increasing consumption of beans, lentils and peas, tomatoes, raisin, dates, and other dried fruit were all associated with significantly decreased prostate cancer risk.     

Risk factors for lung cancer in Iowa women: implications for prevention

BACKGROUND: Multiple risk factors possibly associated with lung cancer were examined as part of a large-scale residential radon case-control study conducted in Iowa between 1994 and 1997. We were particularly interested in stratifying risk factors by smoking status. Relatively little risk factor information is available for Midwestern rural women. METHODS: Four hundred thirteen female lung cancer cases and 614 controls aged 40-84, who were residents of their current home for at least 20 years, were included. Risk factors examined included cigarette smoking, passive smoking, occupation, chemical exposure, previous lung disease, family history of cancer, and urban residence. Multiple logistic regression analysis was conducted after adjusting for age, education, and cumulative radon exposure. RESULTS: As expected, active cigarette smoking was the major risk factor for lung cancer. While cessation of smoking was significantly associated with a reduced risk for lung cancer, the risk remained significantly elevated for 25 years. Among all cases, asbestos exposure was a significant risk. Among ex-smokers, pack-year history predominated as the major risk. Among never smokers, a family history of kidney or bladder cancer were significant risk factors (OR=7.34, 95% CI=1.91-28.18; and OR=5.02, 95% CI=1.64-15.39, respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24-4.18) and asbestos exposure. No statistically significant increase in lung cancer risk was found for occupation or urban residence. CONCLUSIONS: Smoking prevention activities are urgently needed in rural areas of the United States. Relatives of individuals with smoking-related cancers are potentially at increased risk. Genetic risk factors should be more fully investigated in never smokers.     

Epidemiological studies of perinatal carcinogenesis

Epidemiological evidence for prenatal carcinogenesis includes associations between cancer in young people and intrauterine exposure to X-rays, drugs and hormones and prezygotic events such as specific chromosomal aberrations associated with specific cancers. Recent findings suggest that the hormonal environment during early gestation can result not only in the development of clear-cell adenocarcinoma of the vagina but also in the development of germ cell tumours of the testes and ovary. Hormone-related risk factors for testicular germ cell neoplasms include maternal use of exogenous oestrogens during early gestation and, possibly, maternal nausea, maternal obesity and race as well. Ovarian germ cell tumours also appear to be related to maternal use of hormones and obesity. Several epidemiological studies of cancer in young people have been directed towards suggested associations with parental occupational exposures, parental cigarette smoking and household exposures to electric and magnetic fields (EMF). The findings of the many studies of parental occupational exposures are inconsistent and are often nonspecific with respect to the type of childhood cancer and the job exposure implicated. Parental cigarette smoking has been associated in some studies with an increased risk for cancer among children and young adults, and in other studies with an increased risk among mature adults, but the findings are not consistent across studies. Three studies of all types of childhood cancer found risk to be related to household exposures to EMF; in all three, the risk for central nervous system tumours was increased, and in two of the three leukaemia risk as well. A fourth study showed no association between childhood leukaemia and EMF. A hypothesis is proposed which suggests that prenatal and early childhood exposure to N-nitroso compounds (NOC) may be related to the development of primary tumours of the brain in children. Experimentalists have shown that various NOC are potent nervous system carcinogens, particularly when animals are exposed transplacentally. This experimental model and findings from a Los Angeles case-control study (209 pairs) of brain tumours in young people led to the proposed epidemiological hypothesis. Although this and other epidemiological studies of NOC have major limitations, findings from epidemiological studies of congenital defects and of other childhood cancers lend the hypothesis some support. A large international collaborative case-control study of childhood brain tumours was begun recently. This study has a major advantage over most case-control studies in adults because the exposure period of greatest interest (gestation) is clearly defined.     

Case-control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980-2003

The 1984 Windscale study raised concern about a possible association between living in the vicinity of nuclear power plants and childhood cancer. No such effect for all cancers was seen in ecological studies in Germany (1980-1995). Results from exploratory analyses led to a new study. Pre-selected areas around all 16 major nuclear power plants in Germany formed the study area. The design is a matched case-control study; cases are all cancers under five years diagnosed in 1980-2003: 1592 cases, and 4735 controls. Inverse distance of place of residence to the nearest nuclear power plant at the time of diagnosis was used as the independent variable in a conditional logistic regression model. Results show an increased risk for childhood cancer under five years when living near nuclear power plants in Germany. The inner 5-km zone shows an increased risk (odds ratio 1.47; lower one-sided 95% confidence limit 1.16). The effect was largely restricted to leukaemia. The results are compatible with the corresponding subgroups in the previous German ecological studies, with which this study shares most of the cases. They contrast with the lack of an effect observed or expected from other studies due to low doses from routine nuclear power plant operation.     

Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European prospective investigation into cancer and nutrition

The association between childhood environmental tobacco smoke (ETS) exposure and adult cancer risk is controversial; we examined this relationship in never smokers within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Over an average of 10 years, 8,372 cases of cancer were diagnosed in 112,430 never smokers in EPIC. Childhood ETS was self-reported by participants at baseline, along with other lifestyle factors. Hazard ratios (HR) for ETS exposure in childhood and their 95% confidence intervals (CI) were estimated by Cox proportional hazards models stratified by age, sex, and study center and adjusted for education, alcohol drinking, body mass index, physical activity, non-alcoholic energy intake, fruit and vegetable intake, and adulthood ETS exposure. Models were further adjusted for reproductive factors for female cancers, for meat intake for digestive system cancers, and for diabetes status for pancreatic cancer. No association was observed between childhood ETS exposure and overall cancer risks (HR = 0.97, 95% CI = 0.92-1.02), and for selected sites. The only exception was pancreatic cancer, as previously reported by Vrieling et al., among those who had been exposed daily in childhood (overall HR = 2.09, 95% CI = 1.14-3.84). In conclusion, childhood ETS exposure might not be a major risk factor for common cancers in adulthood.