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Biomedical subjects

E Roman

Publications and source records attributed to E Roman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Large tables.

The traditional exploration of large contingency tables leads to multiple comparisons with the inherent generation of chance associations. To allow for this, a simple empirical Bayesian approach is used here to derive estimates of association 'shrunk' towards a global mean. Estimates are displayed on ordered normal plots, to allow visual detection of outliers, with the addition of 'guide rails', derived from simulation, to facilitate their detection. The methods, and the interpretation of results, are illustrated using a large table of occupations for cancer registrations in England and Wales for 1971-90.

Journal Article↗
PubMed2001

Primary infertility in nuclear industry employees: report from the nuclear industry family study.

OBJECTIVE: To determine whether men and women who are occupationally exposed to ionising radiation are at increased risk of primary infertility. METHODS: A cross sectional analysis of reproductive outcome was reported in an occupational cohort of nuclear industry workers from the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels in the United Kingdom. Data on employment and radiation monitoring supplied by employers were linked to data obtained from self administered questionnaires sent to all current employees and a sample of past workers. A total of 5353 men and 603 women aged 40 years or more at the time of survey whose first pregnancy, or attempt at pregnancy, had occurred after first employment in the nuclear industry were recruited to the study. Primary infertility was defined as consultation with a doctor about the failure to achieve at least one viable (24 weeks gestational age or more) pregnancy. RESULTS: 2.6% Of men and 3.7% of women reported primary infertility. For men, this proportion did not differ by amount of radiation monitored or by dose received. The prevalence of infertility was higher among monitored women than non-monitored women, but not significantly so and the numbers were too small to draw any firm conclusions. CONCLUSIONS: No support was found for a hypothesis linking exposure to low level ionising radiation among men with primary infertility. There was weak evidence of an association in women, but the relatively few monitored women prevented detailed examination of these data.

Adult↗
PubMed2000

Fetal death and congenital malformation in babies born to nuclear industry employees: report from the nuclear industry family study.

BACKGROUND: There is some concern about the genetic effects of exposure to low-level ionising radiation, but the evidence is sparse and conflicting. Most work has concentrated on cancer in offspring and little has been done on adverse reproductive outcome. We aimed to assess whether the offspring of men and women who are occupationally exposed to ionising radiation are at increased risk of fetal death and congenital malformation. METHODS: We analysed pregnancies reported by an occupational cohort of nuclear industry workers in the UK, employed at establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. Employment and radiation monitoring data supplied by employers was linked to each pregnancy. FINDINGS: 11,697 men and 1903 women reported one or more singleton pregnancy conceived after first employment within the nuclear industry, the men reporting a total of 23,676 singleton pregnancies and the women 3585. The risks of fetal death and congenital malformation were not related to whether the father had been monitored before conception or to the dose of radiation received. Among pregnancies reported by women, the risk of early (<13 weeks of gestation) miscarriage was higher if the mother had been monitored before conception (odds ratio [OR] 1.3, 95% CI 1.0-1.6), but there was no trend with dose. The risk of stillbirth was also higher if the mother had been monitored before conception (OR 2.2, 95% CI 1.0-4.6), but the finding was based on only 29 cases (13 exposed). The risk of any major malformation, or of specific groups of malformations, was not associated with maternal monitoring, or dose received, before conception. INTERPRETATION: We found no evidence of a link between exposure to low-level ionising radiation before conception and increased risk of adverse reproductive outcome in men working in the nuclear industry. Similarly for women there was no evidence of an association between monitoring before conception and malformation in offspring. The findings relating maternal preconceptual monitoring to increased risk of fetal death are equivocal and require further investigation.

Abnormalities, Radiation-Induced↗
PubMed2000

Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice.

In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.

Alcohol Drinking↗
PubMed2000

Chemical shift resolved photoionization cross sections of amorphous carbon nitride

The various components in the N 1s photoemission spectra of amorphous carbon nitride are identified by measuring their photon energy dependence and comparing the experimental results with ab initio multiple scattering calculations. The intensity modulations with photon energy are due to the extended x-ray absorption fine structure effects.

Journal Article↗
PubMed2000

Residential radon exposure and adult acute leukaemia.

Exposure to radioactive radon gas in homes, from natural sources, is an important public-health issue for many countries. We found no association between household exposure to radon and leukaemia in adults in the UK.

Acute Disease↗
PubMed2000

A pooled analysis of magnetic fields and childhood leukaemia.

Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Adolescent↗
PubMed2000

Polymorphic variation within the glutathione S-transferase genes and risk of adult acute leukaemia.

Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1 and GST P1 affect the body's ability to detoxify a range of potential leukaemogens encountered in the environment. Using PCR, GST T1, GST M1 and GST P1 genotypes were determined in 557 adults with acute leukaemia and 952 age, sex and geographically matched controls. The strongest association with acute leukaemia was observed for the GST T1 null genotype, which occurred among 19% of cases and 14% of controls [odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09-1.93]. A slightly higher proportion of cases (53%) than controls (49%) displayed the GST M1 null genotype, although the difference was not statistically significant (OR 1.22, 95% CI 0.98-1.52). No effect was observed for the GST P1 genotype and no interaction between the GST T1 and GST M1 genotypes was evident. Acute myeloid leukaemia (AML) was weakly associated with both GST T1 null (OR 1.32, 95% CI 0.97-1.79) and GST M1 null (OR 1. 24, 95% CI 0.98-1.56), whereas acute lymphoblastic leukaemia (ALL) was associated with GST T1 null (OR 3.28, 95% CI 1.31-8.26). No associations between smoking and disease risk in relation to GST T1 and GST M1 polymorphic status were found.

Adolescent↗
PubMed2000

Poor metabolizers at the cytochrome P450 2D6 and 2C19 loci are at increased risk of developing adult acute leukaemia.

We have genotyped over 550 cases of acute leukaemia and 950 matched controls from a population-based case-control study, to investigate the impact cytochrome P450s 2D6, 2C19 and 1A1 have on susceptibility to adult acute leukaemia. Analysis included potential associations between polymorphic status and acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), plus the FAB and cytogenetic subtypes therein. A significant increased risk was found for CYP2D6 poor metabolizer phenotype and acute leukaemia [odds ratio (OR) = 1.69, 95% confidence interval (CI) 1.17-2.43], a risk also found in AML and ALL. No interaction was found with smoking. However, a significant age-related association between CYP2D6 polymorphism and acute myeloid leukaemia implied that the excess risk was confined to persons aged 40 years and over (OR 2.38, 95% CI 1.53-3.71). Amongst AML cases, increased odds ratios were observed in both de-novo (OR 1.54, 95% CI 1.02-2.32) and secondary leukaemia (OR 2.83, 95% CI 0.91-8.77), and among patients with a chromosomal abnormality (OR 2.00, 95% CI 1.11-3.61). An increased risk was found for the CYP2C19 poor metabolizer phenotype (OR 1.68, 95% CI 0.97-2.92) which was also present in AML and ALL. For this CYP450 locus, an increased risk was suggested in secondary leukaemia (OR 2.67, 95% CI 0.44-16.3) and amongst AML cases with a chromosomal abnormality (OR 6.72, 95% CI 2.22-20.4). No difference in CYP1A1 genotype distribution was found for acute leukaemia, AML, ALL or any other diagnostic classification group used. No significant interactions between CYP2D6, CYP2C19 or CYP1A1 were found.

Acute Disease↗
PubMed2000

High-producer haplotypes of tumor necrosis factor alpha and lymphotoxin alpha are associated with an increased risk of myeloma and have an improved progression-free survival after treatment.

PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis factor alpha (TNFalpha) and lymphotoxin alpha (LTalpha) genes on the predisposition to myeloma and the effect of these polymorphisms on response to treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was determined in 63 patients with monoclonal gammopathy of uncertain significance (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex-matched population-based controls. The effect on treatment response and survival was determined in 171 myeloma patients treated with either conventional or high-dose chemotherapy. RESULTS: Comparison of the extended TNFalpha/LTalpha haplotype in the myeloma cases and controls showed a significant excess of high-producer alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present in 35.8% of cases but in only 18% of the controls; this presence was associated with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases, suggesting that this genotype is associated with the initiation of plasma-cell disorders rather than the progression of MGUS to myeloma. The median overall survival time of myeloma patients was 53.8 months and showed no difference with regard to TNFalpha/LTalpha polymorphic status. A trend toward an improved progression-free survival was apparent in cases with a high-producer haplotype, although this effect was seen only in patients receiving high-dose chemotherapy. CONCLUSION: Individuals with polymorphisms associated with a high production of TNFalpha/LTalpha are at a significantly increased risk of developing MGUS and myeloma. The impact of polymorphic status on overall survival is minimal, although there is a trend toward an increased progression-free survival in the high-producer group.

Adult↗
PubMed2000

Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models.

In humans, cancer may be caused by genetics and environmental exposures; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues.

Adult↗
PubMed2000

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Adolescent↗
PubMed1999

Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults.

Reduction of 5,10-methylenetetrahydrofolate (methyleneTHF), a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate (methylTHF), the primary methyl donor for methionine synthesis, is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR). A common 677 C --> T polymorphism in the MTHFR gene results in thermolability and reduced MTHFR activity that decreases the pool of methylTHF and increases the pool of methyleneTHF. Recently, another polymorphism in MTHFR (1298 A --> C) has been identified that also results in diminished enzyme activity. We tested whether carriers of these variant alleles are protected from adult acute leukemia. We analyzed DNA from a case-control study in the United Kingdom of 308 adult acute leukemia patients and 491 age- and sex-matched controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. The MTHFR 677TT genotype was lower among 71 acute lymphocytic leukemia (ALL) cases compared with 114 controls, conferring a 4.3-fold decrease in risk of ALL [odds ratio (OR = 0.23; 95% CI = 0.06-0.81]. We observed a 3-fold reduction in risk of ALL in individuals with the MTHFR 1298AC polymorphism (OR = 0.33; 95% CI = 0.15-0.73) and a 14-fold decreased risk of ALL in those with the MTHFR 1298CC variant allele (OR = 0.07; 95% CI = 0.00-1.77). In acute myeloid leukemia, no significant difference in MTHFR 677 and 1298 genotype frequencies was observed between 237 cases and 377 controls. Individuals with the MTHFR 677TT, 1298AC, and 1298CC genotypes have a decreased risk of adult ALL, but not acute myeloid leukemia, which suggests that folate inadequacy may play a key role in the development of ALL.

Acute Disease↗
PubMed1999

Cancer in children of nuclear industry employees: report on children aged under 25 years from nuclear industry family study.

OBJECTIVE: To determine whether children of men and women occupationally exposed to ionising radiation are at increased risk of developing leukaemia or other cancers before their 25th birthday. DESIGN: Cohort study of children of nuclear industry employees. SETTING: Nuclear establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. SUBJECTS: 39 557 children of male employees and 8883 children of female employees. MAIN OUTCOME MEASURES: Cancer incidence in offspring reported by parents. Employment and radiation monitoring data (including annual external dose) supplied by the nuclear authorities. RESULTS: 111 cancers were reported, of which 28 were leukaemia. The estimated standardised incidence ratios for children of male and female employees who were born in 1965 or later were 98 (95% confidence interval 73 to 129) and 96 (50 to 168) for all malignancies and 109 (61 to 180) and 95 (20 to 277) for leukaemia. The leukaemia rate in children whose fathers had accumulated a preconceptual dose of >/=100 mSv was 5.8 times that in children conceived before their fathers' employment in the nuclear industry (95% confidence interval 1.3 to 24.8) but this was based on only three exposed cases. Two of these cases were included in the west Cumbrian ("Gardner") case-control study. No significant trends were found between increasing dose and leukaemia. CONCLUSIONS: Cancer in young people is rare, and our results are based on small numbers of events. Overall, the findings suggest that the incidence of cancer and leukaemia among children of nuclear industry employees is similar to that in the general population. The possibility that exposure of fathers to relatively high doses of ionising radiation before their child's conception might be related to an increased risk of leukaemia in their offspring could not be disproved, but this result was based on only three cases, two of which have been previously reported. High conceptual doses are rare, and even if the occupational association were causal, the number of leukaemias involved would be small; in this study of over 46 000 children, fewer than three leukaemias could potentially be attributed to such an exposure.

Adolescent↗
PubMed1999

Women's occupation and cancer: preliminary analysis of cancer registrations in England and Wales, 1971-1990.

BACKGROUND: In recent years increasing attention has been paid to examining the relation between women's health and their own occupation. The findings presented here relate to an analysis of 381,915 cancers in women registered in England and Wales over the 20-year period 1971-1990. METHODS: To explore the value of the data for epidemiological research, five sites (pleura, bladder, stomach, lung, and breast) and two occupations (agriculture and textile) were selected. Associations between cancer and occupation were evaluated using age and social class adjusted proportional registration ratios (PRRs) and 95% confidence intervals (CI). RESULTS: Pleural cancer risk was increased in a range of occupations with a potential for asbestos exposure (e.g., PRR 608, 95% CI 381-921 for craft and other production process workers), and the well-established link between bladder cancer and employment in the rubber industry was confirmed (PRR 303, 95% CI 188-464). Associations between "dusty" occupations and stomach cancer were noted (e.g., PRR 198, 95% CI 126-298 for ceramic decorators and finishers), and possible links with lung cancer and smoke in the work environment were highlighted (e.g., PRR 167, 95% CI 147-189 for publicans). As a group, agricultural workers were found to be at increased risk of non-Hodgkin's lymphoma (PRR 164, 95% CI 126-211), and textile workers at increased risk of pleural cancer (PRR 145, 95% CI 111-185). No evidence for an occupational aetiology for breast cancer was found within these data. CONCLUSIONS: Occupational information collected at cancer registration in the United Kingdom can be reliably used to identify groups that may be at increased risk of disease.

Adult↗