Relative Risk Of Leukemia Research Articles

Myeloid leukemia risk assessment and dynamics of the granulocytopoietic system in acutely and continuously irradiated humans: modeling approach.

A dynamic modeling approach to the risk assessment of radiogenic myeloid leukemia is proposed. A basic tool of this approach is a biologically motivated mathematical model of the granulocytopoietic system, which is capable of predicting the dynamics of blood granulocytes and bone marrow granulocytopoietic cells in acutely and chronically irradiated humans. The performed modeling studies revealed that the dose dependence of the scaled maximal concentration of bone marrow granulocytopoietic cells with radiation-induced changes, which make a cell premalignant, and the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to acute irradiation conform to the dose dependence of excess relative risk for myeloid leukemia among atomic bomb survivors in a wide range of doses and in a range of comparatively low doses, respectively. Additionally, the dose dependence of the scaled integral of the concentration of these cells over the period of the response of the granulocytopoietic system to continuous irradiation with the dose rate and durations, which were used in brachytherapy, conforms to the dose dependence of excess relative risk for leukemia among the respective groups of exposed patients. These modeling findings demonstrate the potential to use the proposed modeling approach for predicting the excess relative risk for myeloid leukemia among humans exposed to various radiation regimes. Obviously, this is especially important in the assessment of the risks for radiogenic myeloid leukemia among people residing in contaminated areas after an accident or explosion of a radiological device, among astronauts on long-term space missions, as well as among patients treated with radiotherapy.

Age related risk of myelodysplastic syndrome and acute myeloid leukemia among breast cancer survivors

Increased incidence of acute myeloid leukemia (AML) has been identified among breast cancer (BC) survivors but measurement has not included myelodysplastic syndrome (MDS). Our aim is to identify age and stage related MDS/AML incidence post BC diagnosis. We used the 2001-2009 Surveillance, Epidemiology, and end results (SEER) database to identify first primary stage I-III BC patients. Subsequent MDS or AML diagnosis was identified with observed rates compared to expected MDS/AML incidence in the general population. Age adjusted observed/expected rate ratios and 95 % confidence intervals (CI) were calculated. The unadjusted all age and stage MDS/AML incidence rate was .15 % (470/306,691) with a progressively higher rate by age (age 20-49 = .11, age 50-64 = .14, age 65+ =.21, and age 75+ =.18) and stage (stage I = .11, stage II = .18, and stage III = .22). Compared to the general population, BC patients had a 2.75-fold [95 % CI 2.51-3.00] increased relative risk of being diagnosed with MDS/AML. Young age survivors had highest relative risk [age 20-49: relative risk (RR) = 10.60 (95 % CI 8.57-12.93); age 50-64: 5.96 (95 % CI 5.13, 6.88); age 65-74 year-olds: 2.94 (95 % CI 2.45, 3.50); and age ≥75 year-olds: 1.28 (95 % CI 1.03, 1.56)]. Separately MDS relative risk was highest among young women [30.44 (95 % CI = 19.63, 44.62)]. MDS/AML relative risk increased from 1.87 to 5.66 for stage I-III. Myelodysplastic syndrome and acute myeloid leukemia relative risk is substantially elevated among breast cancer survivors especially those aged 20-49. While the actual number is small, MDS/AML is a serious disease. More research is needed to identify the treatments that put women at risk and find less leukemogenic options, especially for young women.

Cancer Risk in Diagnostic Radiation Workers in Korea from 1996–2002

This study was aimed to examine the association between the effective radiation dose of diagnostic radiation workers in Korea and their risk for cancer. A total of 36,394 diagnostic radiation workers (159,189 person-years) were included in this study; the effective dose and cancer incidence were analyzed between the period 1996 and 2002. Median (range) follow-up time was 5.5 (0.04–7) years in males and 3.75 (0.04–7) years in females. Cancer risk related to the average annual effective dose and exposure to more than 5 mSv of annual radiation dose were calculated by the Cox proportional hazard model adjusted for occupation and age at the last follow-up. The standardized incidence ratio of cancer in radiation workers showed strong healthy worker effects in both male and female workers. The relative risk of all cancers from exposure of the average annual effective dose in the highest quartile (upper 75% or more of radiation dose) was 2.14 in male workers (95% CI: 1.48–3.10, p-trend: <0.0001) and 4.43 in female workers (95% CI: 2.17–9.04, p-trend: <0.0001), compared to those in the lower three quartiles of radiation exposure dose (less than upper 75% of radiation dose). Cancer risks of the brain (HR: 17.38, 95% CI: 1.05–287.8, p-trend: 0.04) and thyroid (HR: 3.88, 95% CI: 1.09–13.75, p-trend: 0.01) in female workers were significantly higher in the highest quartile group of radiation exposure compared to those in the lower three quartiles, and the risk of colon and rectum cancers in male workers showed a significantly increasing trend according to the increase of the average annual radiation dose (HR: 2.37, 95% CI: 0.99–5.67, p-trend: 0.02). The relative risk of leukemia in male workers and that of brain cancer in female workers were significantly higher in the group of people who had been exposed to more than 5 mSv/year than those exposed to less than 5 mSv/year (HR: 11.75, 95% CI: 1.08–128.20; HR: 63.11, 95% CI: 3.70–1,075.00, respectively). Although the present study involved a relatively young population and a short follow-up time, statistically significant increased risks of some cancers in radiation workers were found, which warrants a longer follow-up study and more intensive protective measures in this population.

Second Primary Malignancy Risk After Radioactive Iodine Treatment for Thyroid Cancer: A Systematic Review and Meta-analysis

The risk of second primary malignancies (SPMs) associated with cancer therapies is an important concern of thyroid cancer survivors and physicians. Our objective was to determine if the risk of SPMs is increased in individuals with thyroid cancer treated with radioactive iodine (RAI), compared to those not treated with RAI. We performed a systematic review of the literature and meta-analysis. Two independent reviewers screened citations and reviewed full-text papers. If not reported by the primary authors, the relative risk (RR) of SPMs was calculated by dividing the standardized incidence ratio of SPM in individuals with thyroid cancer treated with RAI compared to those not treated with RAI (with associated 95% confidence intervals [CI]). The natural logarithms of RRs of respective SPMs, weighted by the inverse of the variance, were pooled using fixed effects models and the exponential of the results was reported. Two multi-center studies (one from Europe and the other from North America) were included in this review. The RR of SPMs in thyroid cancer survivors treated with RAI was significantly increased at 1.19 (95% confidence interval [CI] 1.04, 1.36, p = 0.010), relative to thyroid cancer survivors not treated with RAI (data from 16,502 individuals), using a minimum latency period of 2 to 3 years after thyroid cancer diagnosis. The RR of leukemia was also significantly increased in thyroid cancer survivors treated with RAI, with an RR of 2.5 (95% CI 1.13, 5.53, p = 0.024). We did not observe a significantly increased risk of the following cancers related to prior RAI treatment: bladder, breast, central nervous system, colon and rectum, digestive tract, stomach, pancreas, kidney (and renal pelvis), lung, or melanoma of skin. The risk of SPMs in thyroid cancer survivors treated with RAI is slightly increased compared to thyroid cancer survivors not treated with RAI.

Risk of Leukemia among Survivors of Testicular Cancer: A Population-Based Study of 40,576 Patients

Survivors of testicular cancer are at increased risk of developing leukemia. We quantify long-term temporal trends in excess absolute risk (EAR) and excess relative risk (ERR) of leukemia among testicular cancer survivors, using multivariate analyses to evaluate the effects of age at diagnosis, attained age, calendar year of testicular cancer diagnosis, time since diagnosis, and initial treatment. A total of 40,576 1-year survivors of testicular cancer were identified within 14 population-based cancer registries in Europe and North America between January 1, 1943 and December 31, 2001. We used Poisson regression analysis to model EAR (per 100,000 person-years) and ERR of secondary leukemia. Cumulative risks were calculated using a competing risk model. Secondary leukemia (excluding chronic lymphocytic leukemia) developed in 89 patients (EAR=10.5, 95% confidence interval (CI)=7.3–14.3; ERR=1.5, 95% CI=1.0–2.1). Significantly elevated risks were observed for acute myeloid leukemia (AML) (EAR=7.1, 95% CI=4.6–10.1; ERR=2.0, 95% CI=1.3–2.9) and acute lymphoblastic leukemia (EAR=1.4, 95% CI=0.4–2.9; ERR=2.1, 95% CI=0.5–4.4). Risk of leukemia was highest during the first 5 years after testicular cancer diagnosis. In analyses adjusted for age at diagnosis and time since testicular cancer diagnosis, the risk of AML was non-significantly higher among patients whose initial management included chemotherapy compared to those who received radiotherapy alone ( p =0.2). Cumulative risk of leukemia was approximately 0.23% by 30 years after testicular cancer diagnosis. Although the relative risk of leukemia is large, the absolute risk and cumulative risk of leukemia following testicular cancer is small. Thus, improvements in survival due to treatment greatly outweigh the risk of this late effect.

Environmental and Behavioral Factors and the Risk of Non-Hodgkin Lymphoma

Investigators around the world have reported that incidence and mortality rates for non-Hodgkin lymphoma (NHL) increased steadily and substantially over the last five decades of the 20th century. Identifying what changes in the environment or in behavior fueled this epidemic still presents a major

Melanoma and Ionizing Radiation: Is There a Causal Relationship?

This review was initiated in response to concerns that ionizing radiation could be a cause of melanoma. Studies presenting the relative risks for melanoma after external ionizing radiation exposure were in seven categories: (1) The Canadian Radiation Dose Registry, (2) nuclear industry workers, (3) subjects near nuclear test blasts, (4) survivors of the atomic bombings of Japan, (5) airline pilots and cabin attendants, (6) recipients of medical radiation, and (7) radiological technicians. Relative risks for leukemia in each of the studies were used to confirm the likelihood of exposure to ionizing radiation. When studies within a category were compatible, meta-analytic methods were used to obtain combined estimates of the relative risk, and a meta-regression analysis of melanoma relative risk compared to leukemia relative risk was used to examine consistency across exposure categories. Generally, exposure categories with elevated relative risks of leukemia had proportionately elevated relative risks of melanoma. This suggests that people exposed to ionizing radiation may be at increased risk of developing melanoma, although alternative explanations are possible. Future epidemiological studies of ionizing radiation effects should include melanoma as an outcome of interest.

Cancer mortality among workers in formaldehyde industries

Formaldehyde exposure has been inconsistently associated in industrial workers with cancer of the nasal cavities, nasopharynx, prostate, lung, and pancreas. Increased risks for leukemia and brain cancer have been found in medical workers and other professionals exposed to formaldehyde. Animals exposed to formaldehyde show excesses of nasal cancer. We evaluated these associations in an updated follow-up of the largest cohort to date of formaldehyde-exposed workers. We evaluated quantitative estimates of formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and cancer mortality (2099 deaths) among 25,619 workers (865,708 person-years) employed in 10 U.S. formaldehyde-producing or -using facilities through 1995 using relative risks (RR) based on Poisson regression. The RRs for nasopharyngeal cancer (9 deaths) increased with average exposure intensity, cumulative exposure, highest peak exposure, and duration of exposure to formaldehyde (Ptrend = 0.066, 0.025, <0.001, and 0.147, respectively). No clear associations with formaldehyde exposure were seen for cancers of the lung (744 deaths), pancreas (93 deaths), brain (62 deaths), or prostate (145 deaths), although RRs for prostate cancer were elevated for some measures of formaldehyde exposure. RRs for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with peak exposure (Ptrend = 0.009) and average exposure intensity (Ptrend = 0.088). RRs for leukemia were not associated with cumulative exposure; they were weakly associated with duration of exposure. In the extended follow-up of this cohort of formaldehyde industry workers, we found an exposure–response relationship with mortality from leukemia, particularly myeloid leukemia, and cancer of the nasopharynx, but no clear association with cancers of the pancreas, brain, lung, or prostate.

Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries.

Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions.

Parental cigarette smoking and the risk of acute leukemia in children

Studies of the relation between parental smoking and childhood leukemia have produced inconsistent results. In the largest case-control studies of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) conducted to date, the authors evaluated leukemia risk relative to parental self-report of cigarette smoking. In telephone interviews in which a structured questionnaire was used, parents of 1842 ALL patients, 517 AML patients, and their matched controls were asked about their cigarette smoking habits before, during, and after the pregnancy with the index child. Risk of leukemia was examined by histologic type, age of the child at diagnosis, immunophenotype (for ALL), and French-American-British morphology group (for AML). The risk of ALL was not associated with the father's ever having smoked (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.90-1.20) or the mother's ever having smoked (OR = 1.04, 95% CI 0.91-1.19). Similarly, no significant risk of AML was observed for paternal (OR = 0.88, 95% CI 0.67-1.16) or maternal smoking (OR = 0.95, 95% CI 0.74-1.22). The relative risk of leukemia was not significantly different from the null for parental smoking in any time period during or around the index pregnancy, nor was it related to the number of cigarettes, the number of years of smoking, or the number of pack-years. A small number of sporadic, statistically significant associations were found, but overall there appeared to be no association between parental cigarette smoking and ALL or AML, or any subgroup of leukemia. Parental smoking while pregnant or exposure to cigarette smoke shortly after birth is unlikely to contribute substantially to the risk of childhood leukemia in North America.

Risk of Leukemia after Platinum-Based Chemotherapy for Ovarian Cancer

Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.

Reactive chemicals and cancer.

Epidemiologic evidence on the relation between reactive chemicals and cancer is reviewed. These highly reactive chemicals (acrylonitrile; bis[chloromethyl]ether and chloromethyl methyl ether; 1,3-butadiene, ethylene oxide; formaldehyde; mustard gas; sulfuric acid; and vinyl chloride) vary in use and exposure. All are animal carcinogens that also have received considerable epidemiologic attention. Acrylonitrile is a chemical of current economic importance. The epidemiologic evidence is quite weak, but the available studies were very small. Epidemiologic studies clearly demonstrate that bis (chloromethyl) ether and chloromethyl methyl ether cause lung cancer. Continued follow-up of exposed workers is encouraged to provide information on risks for other cancers. Results from epidemiologic studies of butadiene-exposed workers are somewhat inconsistent, but the largest study with the best exposure assessment found the largest relative risk for leukemia. The failure of several larger studies to replicate the early Swedish findings of a very strong association between leukemia and ethylene oxide has not been adequately explained. Epidemiologic studies of formaldehyde provide limited evidence for an association with cancer of the nasopharynx and possibly with nasal cancer. These very rare tumors, however, are difficult to study epidemiologically. Mustard gas is a well-established lung carcinogen, but a recent follow-up of the English cohort suggests that other sites also may be affected. Sulfuric acid appears to cause laryngeal cancer. A suggested relationship with lung cancer in a few studies is of concern because of the widespread opportunity for exposure from ambient air pollution. Vinyl chloride causes angiosarcoma of the liver, but a large, multi-country study provided no clear evidence that other sites are affected.

Diamond-Blackfan Anemia Natural History and Sequelae of Treatment

To define further the natural history of treated Diamond-Blackfan anemia (DBA), a congenital anemia characterized by a paucity of erythroid precursors, we analyzed 76 patients diagnosed or followed at Children's Hospital, Boston, between 1931 and 1992. Although DBA is generally defined as macrocytic, we found that mean corpuscular volume in infants aged <5 months rarely exceeded the normal range and is of little diagnostic value. Macrocytosis in patients aged > or = 5 months was more striking. Nine of 16 patients who never received steroids experienced remissions, sometimes after years of transfusions. Thirty-one of 56 patients receiving corticosteroids responded. Of these 31, 13 experienced remissions, 11 remained steroid dependent and 7 later required transfusions. Most nonresponders maintained transfusion dependence. Patients frequently (64%) experienced treatment-related morbidity, most commonly hemosiderosis. The relative risk of leukemia was profoundly elevated (RR, 200; 95% CI, 54.5-512.1) and hematologic parameters at long-term follow-up were often abnormal. While potential responsiveness to steroids and relative ease of red cell transfusion make DBA one of the most treatable congenital marrow failure syndromes, both disease-related and treatment-related factors contributed to a limited prognosis (median survival, 38 years). Patients should be carefully monitored longitudinally for evidence of leukemia and adverse effects of therapy, and alternative treatment strategies should be considered on an individual basis.

Leukemia Risk Associated with Benzene Exposure in the Pliofilm Cohort: I. Mortality Update and Exposure Distribution

The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.

Risk of Leukemia After Treatment With Pituitary Growth Hormone

To determine whether pituitary-derived human growth hormone treatment increases the subsequent risk of developing leukemia and lymphoma. Cohort study. United States. A total of 6284 recipients of pituitary-derived human growth hormone distributed by the National Hormone and Pituitary Program between 1963 and 1985. Leukemia and lymphoma. Three cases of leukemia occurred in 59,736 patient-years of follow-up from the start of growth hormone therapy to case ascertainment at interview; this number was not significantly higher (P = .23) than the 1.66 cases expected in the US age-, race-, and gender-matched general population. Three additional cases, found in an extended follow-up that provided 83,917 person-years of risk, yielded a minimum rate of leukemia that was significantly increased (six cases found, 2.26 expected; P = .028). The relative risk of leukemia in pituitary growth hormone recipients compared with the general population was 1.8 (90% confidence interval [CI], 0.82 to 7.5) for the defined follow-up and 2.6 (90% CI, 1.2 to 5.2) for the extended follow-up. Five of the six subjects who developed leukemia had antecedent cranial tumors (four craniopharyngioma, one astrocytoma) as the cause of growth hormone deficiency, and four had received radiotherapy. There was no increase in leukemia in patients with idiopathic growth hormone deficiency. The association of leukemia and craniopharyngioma was significant (P < .001). There was no excess of lymphoma in the cohort. This cohort of growth hormone recipients had a significantly increased rate of leukemia compared with the age-, race-, and gender-matched general population. However, the upper bound CI of the relative risk in our population (5.2) is well below the other estimates (7.6). Compared with the general population, our study population had more possible risk factors for leukemia (radiation, tumor) that may have contributed to the excess observed. The clustering of cases of leukemia in craniopharyngioma patients should be further evaluated.

A comparison of the risks of leukaemia in the offspring of the Japanese bomb survivors and those of the Sellafield workforce with those in the offspring of the Ontario and Scottish workforces

The cases of childhood leukaemia found among children of the Sellafield (West Cumbria), Ontario and Scottish radiation workers and those observed in the offspring of the Japanese bomb survivors are analysed using exponential and linear forms of a relative risk model and employing dose estimates both for the period 6 months before conception and for total pre-conception doses. Because of the uncertainties that surround the neutron dose estimates in the Hiroshima bomb survivors, analyses of the possible discrepancies between the pre-conception exposure risks of leukaemia in the Japanese and other datasets are performed separately for each city within the Japanese F1 cohort. In general, the discrepancy between the leukaemia relative risk coefficients in the Japanese and West Cumbrian datasets is strongest for Hiroshima, although there are also indications of differences in risks between the West Cumbrian and Nagasaki data. The leukaemia relative risk coefficients for paternal (whole-body) exposure in these pre-conception periods for children in the Canadian and Scottish groups are found to be statistically compatible with the (gonadal dose) coefficients derived from studies of the offspring of the Japanese bomb survivors, whether for each city considered separately or for both cities taken together. There are indications at borderline levels of statistical significance that the leukaemia risks observed in the Canadian and Scottish datasets are not compatible with those derived from the West Cumbrian group, whether for 6-month or total pre-conception dose. Given the lack of a discernibly raised risk of childhood leukaemia in the offspring of the Japanese bomb survivors and the Canadian and Scottish studies, it therefore appears unlikely that the statistical association between recorded paternal pre-conception external radiation and the raised incidence of childhood leukaemia found in the West Cumbrian study represents a causal relationship.

2 - Down syndrome and chromosome 21 abnormalities in leukaemia

Numerical and structural chromosome 21 abnormalities are associated with specific haematological neoplasms (Mitelman, 1988; Sandberg, 1990), thus suggesting the involvement of one or more genes on chromosome 21 in the control of cell growth and differentiation. The first indirect hint of an association between chromosome 21 and leukaemia comes from epidemiological data, showing that the relative risk of leukaemia in children with trisomy 21 and Down syndrome is 10-20 times higher than that of normal children (Fong and Brodeur, 1987; Zipursky et aI, 1987). The observation that trisomy 21cells are the ones involved in the leukaemic transformation in Down syndrome mosaics, and the observation that trisomy 21 is also common in acute lymphocytic (ALL) and myelogenous (AML) leukaemias in non-Down individuals made Rowley (1981) suggest an aetiological role for trisomy 21 in leukaemogenesis. However, acute leukaemia has also been reported in individuals with monosomy of the 21q22 region due to the germ-line inheritance of a ring chromosome 21. A few specificchromosome abnormalities involving chromosome 21 are also consistently associated with AML occurring in both children and adults. The most common is the t(8;21)(q22;q22) in AML with undifferentiated phenotype (Rowley, 1973). The situations in which chromosome 21 is involved are apparently diverse. Our current knowledge of the structure and genetic content of chromosome 21, as well as the recognition that genetic and cellular mechanisms such as genome imprinting and protein-protein interactions are also involved in producing cancer, may help us to unravel the molecular basis of leukaemias involving the smallest human autosome.

A comparison of the risks of childhood leukaemia from parental pre-conception exposure to radiation in the Sellafield and Dounreay workforces and the Japanese bomb survivors

The cases of childhood leukaemia found among children of the Sellafield (West Cumbria) and Dounreay (Caithness) workforces and those observed in the offspring of the Japanese bomb survivors are analysed using exponential and linear forms of a relative risk model and employing dose estimates both for the period six months pre-conception and also for total pre-conception doses. The leukaemia relative risk coefficients for paternal (whole-body) exposure in these pre-conception periods for children in Caithness are found to be statistically compatible with those of the children of Sellafield workers but also with the (gonadal dose) coefficients applying to the offspring of the bomb survivors. These findings are relatively robust to dosimetric uncertainties in the group of Caithness fathers. The Dounreay study has low statistical power and consequently provides little information that is capable of shedding light on the question of a causal link between paternal pre-conception radiation exposure and the incidence of childhood leukaemia in offspring.

Leukemia among Nuclear Workers with Protracted Exposure to Low-Dose Ionizing Radiation

We conducted an analysis of leukemia mortality and protracted exposure to low-dose ionizing radiation. We used data from seven published epidemiologic studies of nuclear workers that reported individual monitoring information for radiation exposure. We found 83 leukemia deaths among white males from a combined total of more than 1.4 million person-years. We calculated an overall relative risk for leukemia of 1.5, after adjustment for age and calendar time, for workers with cumulative occupational doses of 10 mSv (1 rem) or greater, compared with those with cumulative doses of less than 10 mSv. An adjusted relative risk of 1.8 was observed when individuals with 10-50 mSv (1-5 rem) were compared with those who had cumulative occupational doses of less than 10 mSv. The adjusted relative risk for those with doses greater than 50 mSv relative to those with doses less than 10 mSv was 1.2, although the data were especially sparse in this dose range. These combined data indicate a small elevated risk of leukemia for doses of ionizing radiation under 50 mSv.

A comparison of the apparent risks of childhood leukaemia from parental exposure to radiation in the six months prior to conception in the Sellafield workforce and the Japanese bomb survivors

The cases of childhood leukaemia found among children of the Sellafield workforce and those observed in the offspring of the Japanese bomb survivors are analysed using both exponential and linear forms of a relative risk model and employing dose estimates for the period six months pre-conception. The leukaemia relative risk coefficients for paternal (whole-body) exposure in this pre-conception period for children of Sellafield workers are found to be statistically incompatible with the (gonadal dose) coefficients applying to the offspring of the bomb survivors born in the period May 1946 to December 1946, i.e. born 9 to 16 months after the bombings. The incompatibility does not depend on whether the risks in the Japanese children are assumed to be a function simply of paternal gonadal dose or of combined paternal and maternal gonadal dose. This finding is also relatively robust to dosimetric uncertainties in the group of Sellafield fathers and to the addition of extra cases in the offspring of parents in the highest dose groups of both data sets.