Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer.

BACKGROUND: Radiation-related heart disease and lung cancer can occur following radiotherapy for breast cancer but the duration of any mortality risk is uncertain. METHODS: Mortality ratios, by laterality of breast cancer, were estimated using Poisson regression for 558 871 women recorded with breast cancer during 1973-2008 in the Surveillance, Epidemiology and End Results (SEER) cancer registries and followed until 01 January 2009. RESULTS: For women diagnosed with breast cancer during 1973-1982 and given radiotherapy shortly afterwards, the cardiac mortality ratios, left-sided vs right-sided, were 1.19 (1.03-1.38), 1.35 (1.05-1.73), 1.64 (1.26-2.14) and 1.90 (1.52-2.37) at <10, 10-14, 15-19 and 20+ years since diagnosis (2p for trend: <0.001). The lung cancer mortality ratios, ipsilateral vs contralateral, in these women were 1.05 (0.57-1.94), 2.04 (1.28-3.23) and 3.87 (2.19-6.82) at <10, 10-19 and 20+ years, respectively, (2p for trend: 0.002). For women irradiated during 1983-92 there was evidence of radiation-related mortality for lung cancer, but not for heart disease. For women irradiated since 1993 there is, as yet, little evidence of any radiation-related mortality. CONCLUSION: In this population, the radiation-related risks were larger in the third decade after exposure than during the first two decades.

Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials.

BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials. METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982). FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p<0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p<0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy. INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.

International Variation in Criteria for Internal Mammary Chain Radiotherapy.

AIMS: Evidence has emerged that internal mammary chain (IMC) radiotherapy reduces breast cancer mortality, leading to changes in treatment guidelines. This study investigated current IMC radiotherapy criteria and the percentages of patients irradiated for breast cancer in England who fulfilled them. MATERIALS AND METHODS: A systematic search was undertaken for national guidelines published in English during 2013-2018 presenting criteria for 'consideration of' or 'recommendation for' IMC radiotherapy. Patient and tumour variables were collected for patients who received breast cancer radiotherapy in England during 2012-2016. The percentages of patients fulfilling criteria stipulated in each set of guidelines were calculated. RESULTS: In total, 111 729 women were recorded as receiving adjuvant breast cancer radiotherapy in England during 2012-2016 and full data were available on 48 095 of them. Percentages of patients fulfilling IMC radiotherapy criteria in various national guidelines were: UK Royal College of Radiologists 13% (6035/48 095), UK National Institute for Health and Care Excellence 18% (8816/48 095), Germany 32% (15 646/48 095), Ireland 56% (26 846/48 095) and USA 59% (28 373/48 095). Differences between countries occurred because in Ireland and the USA, treatment may be considered in some node-negative patients, whereas in the UK, treatment is considered if at least four axillary nodes are involved or for high-risk patients with one to three positive nodes. In Germany, treatment may be considered for all node-positive patients. CONCLUSIONS: There is substantial variability between countries in criteria for consideration of IMC radiotherapy, despite guidelines being based on the same evidence. This will probably lead to large variations in practice and resource needs worldwide.

Cardiac risks of breast-cancer radiotherapy: a contemporary view.

For some time, there has been compelling evidence both from randomised-controlled trials and from observational studies, that some of the breast-cancer radiotherapy regimens used in the past have led to increased risk of mortality from heart disease. There is also some evidence that the more recent regimens used in the USA are associated with lower risks than previous ones, but it is not clear whether current regimens are free from cardiac risk, especially in the light of recent evidence from the survivors of the bombings of Hiroshima and Nagasaki, in whom a clear relationship was observed between the risk of mortality from heart disease and radiation dose for doses in the range 0-4 Gy. Mortality from radiation-induced heart disease usually occurs at least a decade after irradiation. Symptomatic heart disease might have a much shorter induction period, but little information about it is available at present. Subclinical vascular abnormalities have been observed within months of irradiation, via myocardial perfusion imaging studies, but little is known about the relationship between these and later overt heart disease. At present, few data relate heart dose and other specific characteristics of breast radiotherapy to cardiac outcome. Further information on these topics is needed to enable estimation of the cardiac risk, that is likely to arise from radiotherapy regimens in current use and from those being considered for future use. Such knowledge would facilitate radiotherapy treatment planning and enable a reduction in cardiac risk while maintaining the known benefit in terms of breast cancer mortality.

A parallel analysis of cancer mortality among atomic bomb survivors and patients with ankylosing spondylitis given X-ray therapy.

Radiation-induced cancer mortality rates among atomic bomb survivors with doses of at least 100 rad and patients with ankylosing spondylitis given X-ray therapy have been compared for the first time. The estimated average mean bone marrow dose for the spondylitics is more than twice that for atomic bomb survivors, and yet spondylitics experienced only half the risk of radiation-induced leukemia of atomic bomb survivors. For sites that were heavily irradiated in the spondylitics, provisional estimates indicate comparable doses in the two studies, and similar levels of cancer risk were observed. For these sites, when information from the studies was combined, there were statistically significant excesses for cancers of the esophagus, stomach, lung, and ovaries, multiple myeloma, other lymphomas, and tumors of the spinal cord and nerves. Very high relative risks (RR's) for tumors of the spinal cord and nerves were observed in both studies. For sites that were lightly irradiated in the spondylitics, in addition to previously documented sites, there was a statistically significant excess of cancers of the liver and gallbladder among atomic bomb survivors. A previous subdivision of cancer sites into radiosensitive and other tissues was not supported by the atomic bomb survivor data. Changes in the rates of radiation-induced cancers with age at exposure and time since exposure were studied and compared with the use of generalized linear modeling of the RR's and also by examination of the excess mortality rates. The level of agreement between the two studies was high; provided it is accepted that the reduced level of leukemia risk in the spondylitics is due to cell sterilization, no inconsistencies were found. For a group of solid tumors selected from heavily irradiated sites in the spondylitics, excess risk increased with both age at exposure and time since exposure and RR decreased with age at exposure, but it did not vary with time since exposure between about 5 and at least 30 years following exposure. The finding of a constant RR with time since exposure did not extend to all remaining neoplasms other than leukemia, because the RR for these neoplasms increased with time since exposure in atomic bomb survivors.

Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies.

BACKGROUND: Exposure to the radioactive gas radon and its progeny (222Rn and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. PURPOSE: This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. METHODS: Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64,209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. RESULTS: For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than 10 years since the start of employment, for other and unspecified cancers (excess relative risk per WLM = 0.22%; 95% CI = 0.08-0.37). CONCLUSIONS: The increases in mortality from stomach and liver cancers and leukemia are unlikely to have been caused by radon, since they are unrelated to cumulative exposure. The association between cumulative exposure and pancreatic cancer seems likely to be a chance finding, while the association between cumulative exposure and other and unspecified cancers was caused by deaths certified as due to carcinomatosis (widespread disseminated cancer throughout the body) that were likely to have been due to lung cancers. This study, therefore, provides considerable evidence that high concentrations of radon in air do not cause a material risk of mortality from cancers other than lung cancer. IMPLICATIONS: Protection standards for radon should continue to be based on consideration of the lung cancer risk alone.

Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe.

BACKGROUND: An association between exposure to environmental tobacco smoke (ETS) and lung cancer risk has been suggested. To evaluate this possible association better, researchers need more precise estimates of risk, the relative contribution of different sources of ETS, and the effect of ETS exposure on different histologic types of lung cancer. To address these issues, we have conducted a case-control study of lung cancer and exposure to ETS in 12 centers from seven European countries. METHODS: A total of 650 patients with lung cancer and 1542 control subjects up to 74 years of age were interviewed about exposure to ETS. Neither case subjects nor control subjects had smoked more than 400 cigarettes in their lifetime. RESULTS: ETS exposure during childhood was not associated with an increased risk of lung cancer (odds ratio [OR] for ever exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response relationship could be demonstrated for cumulative spousal ETS exposure. The OR for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible evidence of increasing risk for increasing duration of exposure. No increase in risk was detected in subjects whose exposure to spousal or workplace ETS ended more than 15 years earlier. Ever exposure to ETS from other sources was not associated with lung cancer risk. Risks from combined exposure to spousal and workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma than for adenocarcinoma, but the differences were not statistically significant. CONCLUSIONS: Our results indicate no association between childhood exposure to ETS and lung cancer risk. We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal and workplace ETS. There was no detectable risk after cessation of exposure.

The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977-99.

BACKGROUND: Previous studies of the development of inhibitors and their impact on mortality have been small. OBJECTIVES: To examine the development of inhibitors in people with hemophilia in the UK and their effect on subsequent mortality. PATIENTS: 6078 males with hemophilia A and 1172 males with hemophilia B registered in the UK Haemophilia Centre Doctors' Organisation database, 1977-98. RESULTS: In severe hemophilia A inhibitors developed at rates of 34.4, 5.2 and 3.8 per 1000 years at ages <5, 5-14 and 15+years; cumulative risks at ages 5 and 75 were 16% and 36%. In hemophilia A the rate of inhibitor development decreased during 1977-90, but increased during the 1990s. In severe hemophilia B inhibitors developed at rates of 13.3 and 0.2 per 1000 years at ages <5 and 5+ and cumulative risks at ages 5 and 75 were 6% and 8%. With HIV, inhibitor development did not increase mortality. In severe hemophilia without HIV, inhibitor development doubled mortality during 1977-92, but during 1993-99 mortality was identical with and without inhibitors. In severe hemophilia without HIV but with inhibitors, mortality from causes involving bleeding decreased during 1977-99 (P = 0.001) as did mortality involving intracranial hemorrhage (P = 0.007). CONCLUSIONS: These data provide estimates of the rate of inhibitor development in hemophilia A and hemophilia B, and they show that the rate of inhibitor development has varied over time, although the reasons for this remain unclear. They also show that in severe hemophilia the substantial increase in mortality previously associated with inhibitors is no longer present.

Ionizing radiation: future etiologic research and preventive strategies.

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies.

Recent results from the study of West Bohemian uranium miners exposed to radon and its progeny.

A brief description is given of the study of West Bohemian uranium miners, and recent and ongoing efforts to improve the quality of the data are summarized. Three recent analyses of the data from the cohort have led to rather different estimates of the excess relative risk of mortality from lung cancer per working-level month. The reasons for these different estimates are described, and it is concluded that estimates of lung cancer risk are strongly influenced by the quality of the exposure estimates, especially by the omission of some exposures accumulated during employment at other uranium mines, following the closure of most of the shafts at the original two mines. The most recent analysis has shown that, in common with other cohorts of radon-exposed miners, the excess relative risk of lung cancer per working-level month is modified by age and time since exposure. An inverse effect of exposure rate was also demonstrated, but it affected only men at very high concentrations and appears to be related to the time pattern of exposure. In addition, the risk was found to differ between the two main mines, possibly due to the influence of arsenic in the dust of the mines.

Radon exposure and cancers other than lung cancer in Swedish iron miners.

Data are presented on the risks of cancers other than lung cancer in a cohort of iron miners from northern Sweden occupationally exposed to elevated levels of the radioactive gas radon. Compared with rates for the four northernmost counties of Sweden, mortality was increased for all cancers other than lung cancer (ratio of observed to expected deaths 1.21, 95% confidence interval 1.03-1.41), stomach cancer (ratio of observed to expected deaths 1.45, 95% confidence interval 1.04-1.98), and rectal cancer (ratio of observed to expected deaths 1.94, 95% confidence interval 1.03-3.31). Despite these overall increases, mortality was not significantly associated with cumulative exposure to radon, either for all cancers other than lung cancer or for any site of cancer other than lung cancer individually. However, the data from this cohort on its own have limited power; and for several sites of cancer the data in this study would be consistent with a radon-related increase. Further study of cancers other than lung cancer in populations exposed to radon is required.

The Chatham Blood Pressure Study. An application of Bayesian growth curve models to a longitudinal study of blood pressure in children.

Recent developments in statistics have produced powerful methods that facilitate the analysis of longitudinal studies. These methods are illustrated by an analysis of a longitudinal study of blood pressure in children. The results of the study show a clear tendency for blood pressure to increase with age, and Asian children tend to have lower blood pressures than their Caucasian counterparts of the same age. There is evidence to support the hypothesis that blood pressures track.

Leukemia mortality after X-ray treatment for ankylosing spondylitis.

Leukemia mortality has been studied in 14,767 adult ankylosing spondylitis patients diagnosed between 1935 and 1957 in the United Kingdom, of whom 13,914 patients received X-ray treatment. By 1 January 1992, there were 60 leukemia deaths among the irradiated patients, almost treble that expected from national rates. Leukemia mortality was not increased among unirradiated patients. Among those irradiated, the ratio of observed to expected deaths for leukemia other than chronic lymphocytic leukemia was greatest in the period 1-5 years after the first treatment (ratio = 11.01, 95% confidence interval 5.26-20.98) and decreased to 1.87 (95% confidence interval 0.94-3.36) in the 25+ year period. There was no significant variation in this ratio with sex or age at first treatment. The ratio for chronic lymphocytic leukemia was slightly but not significantly raised (ratio = 1.44, 95% confidence interval 0.62-2.79). Most irradiated patients received all their exposure within a year. Based on a 1 in 15 random sample, the mean total marrow dose was 4.38 Gy. Doses were nonuniform, with heaviest doses to the lower spine. The risk for nonchronic lymphocytic leukemia was adequately described by a linear-exponential model that allowed for cell sterilization in heavily exposed parts of the marrow and time since exposure. Ten years after first exposure, the linear component of excess relative risk was 12.37 per Gy (95% confidence interval 2.25-52.07), and it was estimated that cell sterilization reduced the excess relative risk by 47% at 1 Gy (95% confidence interval 17%-79%). The average predicted relative risk in the period 1-25 years after exposure to a uniform dose of 1 Gy was 7.00.

Patterns of lung cancer mortality among uranium miners in West Bohemia with varying rates of exposure to radon and its progeny.

Lung cancer mortality in a cohort of 4320 miners first employed during 1948-1959 at the Jáchymov and Horní Slavkov uranium mines in West Bohemia and followed until 1 January 1991 has been studied to gain a greater understanding of the consequences of exposure to radon and its progeny. Among men whose exposure rates never exceeded 10 working levels, excess relative risks per unit exposure were greater in younger men, and exposures received in the periods 15-24, 25-34 and 35+ years previously were found to have 47, 24 and 0% of the effect of exposures 5-14 years previously. Within this low-exposure-rate group excess relative risk increased linearly with time-weighted cumulative exposure and did not depend on exposure rate or duration of exposure. For men who spent less than 20% of their employment at the Jáchymov mine the excess relative risk per working level month was 1.36% (95% confidence interval 0.52-3.54) in the baseline category (age group 55+ and exposure received 5-14 years previously). For men who spent more than 20% of their employment at Jáchymov, the corresponding excess relative risk per working level month was higher by a factor of 1.80 (95% confidence interval 1.27-2.97). The difference may be due to the fact that men who spent more than 20% of their employment at Jáchymov were exposed to the much higher levels of arsenic in the dust at the Jáchymov mine than at other mines. When men with exposure rates above 10 working levels were included in the analysis, patterns of risk were complex and depended on both exposure rate and duration of exposure in addition to the factors mentioned above. If these findings are confirmed elsewhere, calculation of risk estimates for extrapolation to modern occupational or environmental exposures should be based on miners with exposure rates below about 10 working levels. Further investigation is desirable of the influence of dusts containing arsenic on lung cancer risk in miners exposed to radon.

Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis.

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.

Screening for disability in the inner city.

A 10% sample of private households on the electoral register of the London borough of Lambeth was screened for disable persons aged 16 and over, using a postal questionnaire. After three mailings and individual follow-up of non-responders, 87% of the sample households returned questionnaires. Disability was defined in the screening questionnaire as functional limitations or activity restrictions consequent upon disease or impairment. The overall point prevalence of disability was estimated at 15.4% and the most frequently reported impairments were those of the sense organs, bones, central nervous, circulatory, and respiratory systems. Hearing difficulties were the single most frequently reported functional limitation. A log-linear modelling procedure identified age, marital status, and working status as the factors most strongly associated with disability for both men and women. In addition, men aged 50-64 and not working, and men in manual occupations and living alone, were more likely to report disability. These findings indicate that some population groups are disable by functional limitations and activity restrictions not included in office criteria of identification and assessment. These criteria might be broadened, and serves planned for those population groups with higher rates of reported disability.

Completeness of follow up in a cohort study of mortality using the United Kingdom National Health Service Central Registers and records held by the Department of Social Security.

STUDY OBJECTIVE: The aim was to evaluate and improve the completeness of follow up in a cohort study of mortality carried out using the UK National Health Service (NHS) Central Registers. SETTING: This was a follow up study of UK servicemen who served abroad in the 1950s and 1960s, including those who participated in the UK atmospheric nuclear weapon tests and experimental programmes. DESIGN: Details of men for whom follow up achieved using the NHS Central Registers was unsatisfactory were submitted to the Department of Social Security (DSS) for tracing, as were details of men born before 1916 and reported by the NHS Central Registers as currently registered with a general practitioner, and a 1% sample of remaining men born in or after 1916. MEASUREMENTS AND MAIN RESULTS: The additional follow up increased the number of deaths fully identified in the cohort by 6.5%. Mortality among those untraced on the NHS Central Registers was substantially greater than in the cohort as a whole (10.2% v 6.9%). Among those reported by the NHS Central Registers as not currently registered with a general practitioner, 2.7% were found to have died, as were 1.1% of men born before 1916 and currently reported to be registered with a general practitioner. As expected there was clear evidence that information about emigrations supplied by both the NHS Central Registers and DSS is far from complete. CONCLUSION: Standardised mortality ratios based on follow up via the NHS Central Registers alone are likely to be somewhat low, and this should be borne in mind when interpreting the data.

Dominant lethal studies in male mice after exposure to 2.45 GHz microwave radiation.

Adult male mice had the lower halves of their bodies exposed in a waveguide system to 2.45 GHz microwave radiation for 30 min. The half body dose-rate of 43 W kg-1 had been shown in a previous study [7] to deplete severely the heat-sensitive stages of sperm production. The males were mated at intervals to adult hybrid females over the following 8-10 weeks. There was no significant reduction in post-implantation survival, suggesting that the microwave exposure did not have a mutagenic effect on the male germ cells. However, pregnancy rate was significantly reduced in weeks 3, 4, 5 and 6; reaching a minimum of about 10% of the control value in weeks 4 and 5. The occurrence of low values in weeks 4 and 5 correlated well with the expected reductions in sperm count due to the pattern of depletion of the spermatogenic epithelium of the testes. Thus it was concluded that the reduced pregnancy rate resulted from reduced male fertility. Pre-implantation survival can also be affected by reduced sperm count [8] and was significantly reduced in this study but it correlated less well with the anticipated heat response. A further study is in progress looking at the contribution of sperm count and sperm abnormality to the results.