Prostate cancer is an important and growing public health problem. PSA testing is able to lead to the identification of large numbers of cases of prostate cancer while still asymptomatic. This provides the potential for important reductions in prostate cancer mortality through the introduction of screening programs. The most reliable evidence that this potential can be realised can only come from randomised controlled trials (RCTs). Alternative sources of evidence are compared with that from RCTs; the costs of a wrong decision would be high and it is argued that the case for RCTs is clear.

A population-based case–control study of diet, inherited susceptibility and prostate cancer was undertaken in the lowlands and central belt of Scotland to investigate the effect of phyto-oestrogen intake and serum concentrations on prostate cancer risk. A total of 433 cases and 483 controls aged 50–74 years were asked to complete a validated FFQ and provide a non-fasting blood sample. Multivariate logistic regression analysis found significant inverse associations with increased serum concentrations of enterolactone (adjusted OR 0·40, 95 % CI 0·22, 0·71] and with the consumption of soy foods (adjusted OR 0·52, 95 % CI 0·30, 0·91). However, no significant associations were observed for isoflavone intake or serum genistein, daidzein and equol. This study supports the hypotheses that soy foods and enterolactone metabolised from dietary lignans protect against prostate cancer in older Scottish men.

A proportion of Hodgkin lymphoma (HL) cases are causally associated with the Epstein‐Barr virus (EBV) but the aetiology of the remaining cases remains obscure. Over the last 3 decades several studies have found an association between HL and measles virus (MV) including a recent cohort study describing the detection of MV antigens in Hodgkin and Reed‐Sternberg cells, the tumour cells in HL. In the present study we looked at the relationship between history of MV infection and risk of developing HL in a population‐based, case/control study of HL. In addition we used immunohistochemistry and RT‐PCR to look for direct evidence of MV in HL biopsies. There was no significant difference in the proportion of cases reporting previous measles compared to controls in the entire data set or when young adults were considered separately. Using a robust immunohistochemical assay for MV infection, we failed to find evidence of MV in biopsies from 97 cases of HL and RT‐PCR studies similarly gave negative results. This study therefore provides no evidence that MV is directly involved in the development of HL. However, when age at first reported MV infection was investigated, significant differences emerged with children infected before school‐age having higher risk, especially of EBV−ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear. © 2007 Wiley‐Liss, Inc.

The association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients.

A single nucleotide polymorphism (SNP) is present at position -174 of the human interleukin-6 gene. The risk of developing Hodgkin's lymphoma (HL) in young adults decreases with an increasing number of C alleles at this position. We analysed the effect of this SNP on incidence and outcome in HL. DNA samples from 408 cases and 349 controls were screened and analysed following stratification by age, histological subtype and Epstein-Barr virus status. Although the risk of classical HL in young adults decreased with increasing C alleles, case-control differences were not significant. An excess of G alleles was observed for nodular lymphocyte predominant HL in young adults (n = 21), which was significant.

OBJECTIVE:To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK.PARTICIPANTS:6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL).MAIN OUTCOME MEASURE:Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy.RESULTS:Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years.CONCLUSION:These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.

An accumulating body of data suggests that the Epstein-Barr virus (EBV), a lymphotropic herpesvirus, is involved in the pathogenesis of a proportion of cases of Hodgkin lymphoma (HL). In this study, we showed that the frequency of circulating EBV-infected cells was significantly higher (P < 0.001) in pretreatment blood samples from EBV-associated cases when compared with non-EBV-associated cases. We further showed that in patients with EBV-associated disease, the virus persisted in the peripheral blood in memory B cells. This phenotype is consistent with that seen in healthy seropositive controls, post-transplant patients and patients with acute infectious mononucleosis. The data suggest that an increased frequency of EBV carrying B cells in peripheral blood is associated with EBV-associated HL.

In previous studies (Birch et al, 2000; McNally et al, 2002a, 2002b, 2003, 2004) we demonstrated significant space-time clustering amongst cases of ALL, astrocytoma, soft tissue sarcoma and Wilms’ tumour. We hypothesised that there may be a common aetiology particularly between some of these diagnostic groups. The aim of the present study was to test this hypothesis by analysing for cross-clustering between cases in different diagnostic groups.

Somatic inactivation of NFKBIA , the gene encoding IκBα, is a frequent occurrence in the malignant Hodgkin and Reed‐Sternberg (HRS) cells of Hodgkin lymphoma (HL). Impairment of IκBα function results in deregulated NF‐κB activity, a characteristic of HRS cells. The molecular basis for familial HL, which accounts for approximately 4% of all HL cases, is unclear. To date, familial HL cases have not been evaluated for germline NFKBIA mutations. We screened the entire NFKBIA gene in 8 individuals with familial HL but found no mutations in the coding region or promoter sequences. We identified the first germline NFKBIA missense mutation in a patient with presumed sporadic HL. The frequency of 4 polymorphisms within the NFKBIA gene and promoter region was investigated in a series of HL and control samples; no significant differences emerged but a novel polymorphism was identified in the promoter region. Overall, our results suggest that germline mutations of NFKBIA are not a significant cause of familial aggregation of HL but may contribute to inherited susceptibility to HL. © 2005 Wiley‐Liss, Inc.

Objective: To study dietary intake and serum concentrations of isoflavones in order to provide relative validation of isoflavone intake estimates from the Scottish Collaborative Group – Food-Frequency Questionnaire (SCG-FFQ). Design: Validation study. Setting: Southern Scotland. Method: Dietary intake of isoflavones was estimated using the semiquantitative SCG-FFQ and rank correlation and Kappa statistics were used for the relative validation of intakes against serum isoflavone concentrations in 203 male participants who were population controls in a case–control study of diet and prostate cancer. Results: The median intake of isoflavones (daidzein and genistein) was 1.0 mg/day (I-QR 0.6–1.8). The median serum concentration of genistein was 33.79 nmol/l (I-QR 14.12–64.93), nearly twice that of daidzein (18.00 nmol/l, I-QR 8.26–29.45). Equol was detected in 49% of subjects; in these subjects the median was 0.67 nmol/l (I-QR 0.34–1.51). Isoflavone intake was significantly correlated with serum concentrations of daidzein ( ρ =0.24, P =0.001), genistein ( ρ =0.26, P <0.001) and total isoflavonoids (sum of daidzein, genistein and equol) ( ρ =0.27, P <0.001). Whereas values for weighted Kappa ranged from 0.16 ( P =0.002) for daidzein and equol combined to 0.22 ( P <0.001) for genistein. Conclusions: These results demonstrate the suitability of the SCG-FFQ to rank usual isoflavone intakes in older Scottish men, a population observed to have low consumption of soy foods.

We have examined space-time clustering amongst cases of lymphoma in children, aged 0-14 years, using population-based data from the North West of England for the period 1954-2001. There was little or no evidence for space-time clustering amongst all the lymphomas or amongst those sub-groups identified in advance.

Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical HD, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV+ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were performed for the whole age range and separately for young (< 35 years) and old adults (> or = 35 years); formal tests of effect modification by age were included. For the young adults, reported IM in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.08-7.98 and OR = 5.22, 95% CI: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD.

Aims: The epidemiological and pathological features of Hodgkin lymphoma (HL) are complex. The Epstein-Barr virus (EBV) is consistently associated with a proportion of cases, and these cases are thought to represent a distinct aetiological subgroup of HL. The aim of the present analysis was to determine the age and sex specific incidence of EBV associated and non-associated HL, analysed separately, using data derived from a population based study–the Scotland and Newcastle epidemiological study of Hodgkin’s disease (SNEHD). This study also provided a unique opportunity to evaluate accuracy in the current diagnosis and classification of HL. Methods: SNEHD analysed consecutive cases of HL diagnosed in the study area between 1993 and 1997. Diagnostic biopsy material was retrieved, EBV status of tumours was determined, and histological review was performed. Results: In total, 622 cases were eligible for the study, and EBV studies and histopathological review were performed on biopsy material from 537 and 549 cases, respectively. Accuracy in the overall diagnosis of HL and classification of nodular sclerosis HL was good, but diagnosis of HL in the elderly and classification of other subtypes was less reliable. One third of classic HL cases were EBV associated, and age specific incidence curves for EBV associated and non-associated cases were distinct. Conclusions: Comparison of age specific incidence curves for EBV associated and non-associated HL supports the hypothesis that these are two distinct aetiological entities. Accuracy in the diagnosis of HL is generally good, but certain subgroups of cases continue to present diagnostic difficulties.

Aims: To examine pathology characteristics of breast cancers detected by mammography screening over 10 years in Scotland, and compare the nature of cancer yields after different levels of very small invasive cancer at prevalence detection. Methods: A pathology database of cancers from mammography screening of women aged 50–64 years invited every three years was used to assess the variation over time in annual yield of different invasive cancer sizes. Screening centres were compared for incidence screen yields, according to sizes, histological type, grade, and node status. Results: There was a significant trend over time for increased detection of < 15 mm cancers among 2353 prevalence cancers, and a significant trend for increase in all size groups, < 10, 10–14, < 15, and ≥ 15 mm, among 2245 incidence cancers. Based on individual screening centres, there was a significant negative relation between proportions of very small (< 10 mm) cancers at prevalence screens and of large (≥ 15 mm) cancers at incidence screens of the same “cohort” three years later. There was no significant relation on the same centre basis for worse pathology characteristics (histological no special type, high grade, and positive node status) in cancers detected in the same “cohort” three years later. Conclusions: Sensitive mammography screening has a significant effect on the nature of yields at subsequent screens. Length of screening interval and consistency in pathologist opinions are factors that account for lack of effect on incidence cancer qualitative pathology characteristics. These issues are relevant to the use of such characteristics as surrogate measures of service screening performance.

The Epstein‐Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS‐ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit‐and‐run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS‐ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS‐ve HL were more likely to be EBV‐seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS+ve and HRS‐ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit‐and‐run mechanism involving EBV plays a role in the pathogenesis of HL. © 2003 Wiley‐Liss, Inc.

BJU InternationalVolume 92, Issue s2 p. 112-114 Monitoring the ERSPC trial H.J. De Koning, H.J. De Koning Department of Public Health, Erasmus MC, Rotterdam, the Netherlands,Search for more papers by this authorT. Hakulinen, T. Hakulinen Finnish Cancer Registry, Institute for Statistical Cancer Research, Helsinki, Finland,Search for more papers by this authorS.M. Moss, S.M. Moss Royal Cancer Hospital, Institute of Cancer Research, Cancer Screening & Evaluation Unit, Sutton, Surrey, UK,Search for more papers by this authorJ. Adolfsson, J. Adolfsson Center for Surgical Sciences, Karolinska Institute, Stockholm, Sweden,Search for more papers by this authorP.H. Smith, P.H. Smith Consultant Urologist, Leeds, West Yorkshire, UK, andSearch for more papers by this authorF.E. Alexander, F.E. Alexander University of Edinburgh, Department of Public Health, Edinburgh, Scotland, UKSearch for more papers by this authorERSPC, ERSPC Department of Public Health, Erasmus MC, Rotterdam, the Netherlands,Search for more papers by this author H.J. De Koning, H.J. De Koning Department of Public Health, Erasmus MC, Rotterdam, the Netherlands,Search for more papers by this authorT. Hakulinen, T. Hakulinen Finnish Cancer Registry, Institute for Statistical Cancer Research, Helsinki, Finland,Search for more papers by this authorS.M. Moss, S.M. Moss Royal Cancer Hospital, Institute of Cancer Research, Cancer Screening & Evaluation Unit, Sutton, Surrey, UK,Search for more papers by this authorJ. Adolfsson, J. Adolfsson Center for Surgical Sciences, Karolinska Institute, Stockholm, Sweden,Search for more papers by this authorP.H. Smith, P.H. Smith Consultant Urologist, Leeds, West Yorkshire, UK, andSearch for more papers by this authorF.E. Alexander, F.E. Alexander University of Edinburgh, Department of Public Health, Edinburgh, Scotland, UKSearch for more papers by this authorERSPC, ERSPC Department of Public Health, Erasmus MC, Rotterdam, the Netherlands,Search for more papers by this author First published: 13 January 2004 https://doi.org/10.1111/j.1464-410X.2003.4410x.xCitations: 10 H.J. de Koning, Department of Public Health, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, the Netherlands. e-mail: h.dekoning@erasmusmc.nl Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume92, Issues2December 2003Pages 112-114 RelatedInformation

This article reports measurements of household levels of gamma and cosmic rays at the addresses of children with cancer at the time of diagnosis and six months before, and of similar data at the addresses of control children. There is no indication of increased risk with increasing dose rates either in matched or unmatched analyses, with or without adjustment for deprivation. Sub-division by diagnostic group did not reveal any association with any specific types of malignancy. Studies of the relationship between household gamma rays and radon concentration show no evidence of any interactions. (C) 2002 Cancer Research UK.

This paper reports the results of the United Kingdom Childhood Cancer Study relating to risks associated with radon concentrations in participants homes at the time of diagnosis of cancer and for at least 6 months before. Results are given for 2226 case and 3773 control homes. No evidence to support an association between higher radon concentrations and risk of any of the childhood cancers was found. Indeed, evidence of decreasing cancer risks with increasing radon concentrations was observed. Adjustment for deprivation score for area of residence made little difference to this trend and similar patterns were evident in all regions and in all diagnostic groups. The study suggests that control houses had more features, such as double glazing and central heating, leading to higher radon levels than case houses. Further, case houses have features more likely to lead to lower radon levels, e.g. living-rooms above ground level, Consequently the case-control differences could have arisen because of differences between houses associated with deprivation that are not adequately allowed for by the deprivation score. (C) 2002 Cancer Research UK.

To investigate whether infections or other environmental exposures may be involved in the aetiology of childhood central nervous system tumours, we have analysed for space–time clustering and seasonality using population-based data from the North West of England for the period 1954 to 1998. Knox tests for space–time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine changes of incidence with month of birth or diagnosis. There was strong evidence of space–time clustering, particularly involving cases of astrocytoma and ependymoma. Analyses of seasonal variation showed excesses of cases born in the late Autumn or Winter. Results are consistent with a role for infections in a proportion of cases from these diagnostic groups. Further studies are needed to identify putative infectious agents.