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Background: Few prospective studies have examined cancer incidence among vegetarians.Methods: We studied 61,566 British men and women, comprising 32,403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20,601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use.Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07-1.20) in fish eaters and 0.36 (0.16-0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18-0.77) in fish eaters and 0.69 (0.45-1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36-1.81) in fish eaters and 0.47 (0.25-0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56-1.29) in fish eaters and 0.55 (0.39-0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73-0.93) in fish eaters and 0.88 (0.81-0.96) in vegetarians (P for heterogeneity=0.001).Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters. [ABSTRACT FROM AUTHOR]

Background: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function.Methods: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents.Results: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3.Conclusion: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis. [ABSTRACT FROM AUTHOR]

Background: P53, EGFR and HER-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance.Methods: Published studies that investigated the association between p53, EGFR and HER-2/neu status and survival were identified. Meta-analysis was performed using a DerSimonian-Laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis.Results: A total of 62 studies were included for p53, 15 for EGFR and 20 for HER-2/neu. P53, EGFR and HER-2/neu status had a modest effect on overall survival (pooled HR 1.47, 95% CI 1.33-1.61 for p53; HR 1.65, 95% CI 1.25-2.19 for EGFR and HR 1.67, 95% CI 1.34-2.08 for HER-2/neu). Meta-regression analysis for p53 showed that FIGO stage distribution influenced study outcome. For EGFR and HER-2/neu, considerable publication bias was present.Conclusions: Although p53, EGFR and HER-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies. [ABSTRACT FROM AUTHOR]

Background:The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy.Methods:An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated.Results:A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135–759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P=0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir 0.5 μg ml−1 at 12 months, with 57.8% achieving 0.2 μg ml−1. Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 μg ml−1 or negative biopsy if nadir not achieved) after one HIFU session in 92.4% (159 out of 172) of patients.Conclusion:HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment.British Journal of Cancer (2009) 101, 19–26; doi:10.1038/sj.bjc.6605116 www.bjcancer.com Published online online 9 June 2009 [ABSTRACT FROM AUTHOR]

Background: Epigenetic silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) by promoter methylation is associated with improved survival in glioblastomas treated with alkylating agents. In this study, we investigated MGMT promoter methylation in glioblastomas treated with temozolomide and radiotherapy in a single UK treatment centre.Methods: Quantitative methylation data at individual CpG sites were obtained by pyrosequencing for 109 glioblastomas.Results: Median overall survival (OS) was 12.4 months with 2-year survival of 17.9%. Pyrosequencing data were reproducible with archival samples yielding data for all glioblastomas. Variation in methylation patterns of discrete CpG sites and intratumoral methylation heterogeneity were observed. A total of 58 out of 109 glioblastomas showed average methylation >non-neoplastic brain in at least one clinical sample; 86% had homogeneous methylation status in multiple samples. Methylation was an independent prognostic factor associated with prolonged progression-free survival (PFS) and OS. Cases with methylation more than 35% had the longest survival (median PFS 19.2; OS 26.2 months, 2-year survival of 59.7%). Significant differences in PFS were seen between those with intermediate or high methylation and unmethylated cases, whereas cases with low, intermediate or high methylation all showed significantly different OS.Conclusions: These data indicate that MGMT methylation is prognostically significant in glioblastomas given chemoradiotherapy in the routine clinic; furthermore, the extent of methylation may be used to provide additional prognostic stratification. [ABSTRACT FROM AUTHOR]

Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC. [ABSTRACT FROM AUTHOR]

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17 923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87-0.99), 0.65 (0.56-0.76), and 0.75 (0.57-0.98), respectively (P-value for heterogeneity=0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07-1.12), 1.23 (1.17-1.29), and 1.13 (1.03-1.23), respectively (P-value for heterogeneity=0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (P<0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings. [ABSTRACT FROM AUTHOR]

We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin-fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C, 13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG+C and Xelox+C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and 7%. Statistically significant differences were evident for patients receiving Xelox+cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43, P=0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P=0.012). The excess toxicity observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the trial management group to conclude that a capecitabine dose adjustment was required to maintain safety levels when using this regimen. [ABSTRACT FROM AUTHOR]

Population screening for colorectal cancer (CRC) has recently commenced in the United Kingdom supported by the evidence of a number of randomised trials and pilot studies. Certain factors are known to influence screening cost-effectiveness (e.g. compliance), but it remains unclear whether an ageing population (i.e. demographic change) might also have an effect. The aim of this study was to simulate a population-based screening setting using a Markov model and assess the effect of increasing life expectancy on CRC screening cost-effectiveness. A Markov model was constructed that aimed, using a cohort simulation, to estimate the cost-effectiveness of CRC screening in an England and Wales population for two timescales: 2003 (early cohort) and 2033 (late cohort). Four model outcomes were calculated; screened and non-screened cohorts in 2003 and 2033. The screened cohort of men and women aged 60 years were offered biennial unhydrated faecal occult blood testing until the age of 69 years. Life expectancy was assumed to increase by 2.5 years per decade. There were 407 552 fewer people entering the model in the 2033 model due to a lower birth cohort, and population screening saw 30 345 fewer CRC-related deaths over the 50 years of the model. Screening the 2033 cohort cost pound 96 million with cost savings of pound 43 million in terms of detection and treatment and pound 28 million in palliative care costs. After 30 years of follow-up, the cost per life year saved was pound 1544. An identical screening programme in an early cohort (2003) saw a cost per life year saved of pound 1651. Population screening for CRC is costly but enables cost savings in certain areas and a considerable reduction in mortality from CRC. This Markov simulation suggests that the cost-effectiveness of population screening for CRC in the United Kingdom may actually be improved by rising life expectancies. [ABSTRACT FROM AUTHOR]

We investigated infections in early life (diagnosed in general practice) and subsequent risk of childhood leukaemia in the UK General Practice Research Database (GPRD). All children born at GPRD practices and subsequently diagnosed with leukaemia were identified as cases and were individually matched (on year of birth, sex and practice) to up to 20 controls. The final analysis included 162 leukaemia cases and 2215 matched controls. Conditional logistic regression demonstrated no evidence that children with one or more recorded infection in the first year of life had a reduced risk of leukaemia (OR=1.05, 95%CI 0.69, 1.59; P=0.83) or acute lymphoblastic leukaemia (ALL; OR=1.05, 95%CI 0.64-1.74; P=0.84). Our study provides no support for the Greaves hypothesis, which proposes that reduced or delayed exposure to infections in early life increases the risk of childhood ALL. [ABSTRACT FROM AUTHOR]

The purpose of this study was to project mortality rates in the United Kingdom for the period 2006-2025 for 21 major cancers on the basis of the observed trends in mortality rates during 1971-2005, and to estimate the implication in terms of expected deaths. Age-period-cohort models were applied to official statistics. The projected decrease in age-standardised mortality rates for all cancers from 2003 to 2023 was 17% in men and 16% in women. Future mortality rates were projected to decline for most cancer sites. In men, there were small projected increases in mortality rates from cancers of the oral cavity, oesophagus and melanoma, with a larger projected increase (14% over 20 years) in mortality of liver cancer. In women, the only projected increase (18%) was for corpus uteri. The numbers of deaths will increase for most cancers, with a 30% increase in all cancers projected for men and a 12% increase projected for women. Mortality rates from cancer as a whole have been falling in the United Kingdom since 1990, and this decline was projected to continue into the future as well as the declining rates in both sexes for most cancers. Actual numbers of deaths will increase for most cancers. [ABSTRACT FROM AUTHOR]

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Using a model-based approach, we estimated the probability that an individual, with a specified combination of risk factors, would develop lung cancer within a 5-year period. Data from 579 lung cancer cases and 1157 age- and sex-matched population-based controls were available for this analysis. Significant risk factors were fitted into multivariate conditional logistic regression models. The final multivariate model was combined with age-standardised lung cancer incidence data to calculate absolute risk estimates. Combinations of lifestyle risk factors were modelled to create risk profiles. For example, a 77-year-old male non-smoker, with a family history of lung cancer (early onset) and occupational exposure to asbestos has an absolute risk of 3.17% (95% CI, 1.67-5.95). Choosing a 2.5% cutoff to trigger increased surveillance, gave a sensitivity of 0.62 and specificity of 0.70, while a 6.0% cutoff gave a sensitivity of 0.34 and specificity of 0.90. A 10-fold cross validation produced an AUC statistic of 0.70, indicating good discrimination.If independent validation studies confirm these results, the LLP risk models' application as the first stage in an early detection strategy is a logical evolution in patient care. [ABSTRACT FROM AUTHOR]

There is a high and rising prevalence of prostate cancer (PRCA) within the male population of the United Kingdom. Although the relative risk of PRCA is higher in male BRCA2 and BRCA1 mutation carriers, the histological characteristics of this malignancy in these groups have not been clearly defined. We present the histopathological findings in the first UK series of BRCA1 and BRCA2 mutation carriers with PRCA. The archived histopathological tissue sections of 20 BRCA1/2 mutation carriers with PRCA were collected from histopathology laboratories in England, Ireland and Scotland. The cases were matched to a control group by age, stage and serum PSA level of PRCA cases diagnosed in the general population. Following histopathological evaluation and re-grading according to current conventional criteria, Gleason scores of PRCA developed by BRCA1/2 mutation carriers were identified to be significantly higher (Gleason scores 8, 9 or 10, P=0.012) than those in the control group. Since BRCA1/2 mutation carrier status is associated with more aggressive disease, it is a prognostic factor for PRCA outcome. Targeting screening to this population may detect disease at an earlier clinical stage which may therefore be beneficial. [ABSTRACT FROM AUTHOR]

Although anaemia is recognised as a feature of colorectal cancer, the precise risk is unknown. We performed a case-control study using electronic primary care records from the Health Improvement Network database, UK. A total of 6442 patients had a diagnosis of colorectal cancer, and were matched to 45 066 controls on age, sex, and practice. We calculated likelihood ratios and positive predictive values for colorectal cancer in both sexes across 1 g dl(-1) haemoglobin and 10-year age bands, and examined the features of iron deficiency. In men, 178 (5.2%) of 3421 cases and 47 (0.2%) of 23,928 controls had a haemoglobin <9.0 g dl(-1), giving a likelihood ratio (95% confidence interval) of 27 (19, 36). In women, the corresponding figures were 227 (7.5%) of 3021 cases and 58 (0.3%) of 21,138 controls, a likelihood ratio of 41 (30, 61). Positive predictive values increased with age and for each 1 g dl(-1) reduction in haemoglobin. The risk of cancer for current referral guidance was quantified. For men over 60 years with a haemoglobin <11 g dl(-1) and features of iron deficiency, the positive predictive value was 13.3% (9.7, 18) and for women with a haemoglobin <10 g dl(-1) and iron deficiency, the positive predictive value was 7.7% (5.7, 11). Current guidance for urgent investigation of anaemia misses some patients with a moderate risk of cancer, particularly men. [ABSTRACT FROM AUTHOR]

Questionnaires were circulated to UK patients and health care professionals (HCPs) participating in the Taxotere as Adjuvant ChemoTherapy (TACT) trial in autumn 2004 asking if and how trial results, when available, should be conveyed to patients. A total of 1431 (37% of surviving UK TACT patients) returned questionnaires. In all, 30 (2%) patients did not want results. In all, 554 (40%) patients preferred to receive them via their hospital; 664 (47%) preferred results posted directly to their home, 177 (13%) preferred a letter providing a telephone number to request results. Six hundred and twelve patients thought results should come directly from the trials office. One hundred and seventy-six HCPs from 89 UK centres (86%) returned questionnaires. In all, 169 out of 176 patients (96%) thought results should be written in lay terms for patients. Seventy (41%) preferred patients to receive results via their hospital; 64 (38%) preferred a letter providing a telephone number to request results, and 32 (19%) preferred results posted directly to patients. Thirty-one HCPs (18%) thought results to patients should come directly from the trials office. A total of 868 (61%) patients thought next of kin of deceased patients should receive results, 543 (38%) did not; 47 (27%) HCPs thought they should; 118 (68%) did not.British Journal of Cancer (2008) 98, 34–38. doi:10.1038/sj.bjc.6604119 www.bjcancer.com Published online 4 December 2007 [ABSTRACT FROM AUTHOR]

Aspirin may reduce the risk of cancer at some sites but its effect at the lung is unclear. We prospectively examined associations between aspirin use and risk of lung cancer in 109,348 women in the Nurses' Health study from 1980 to 2004. During this time, 1,360 lung cancers were documented in participants 36-82 years of age. Aspirin use and smoking were assessed every 2 years. Risk of lung cancer was a non-significant 16% lower for regular aspirin users of one or two tablets per week and a significant 55% higher for users of 15 or more tablets per week compared with women who never regularly used aspirin. Results were similar when limited to never smokers. For both the low and high quantity aspirin users, risk of lung cancer did not decline or increase with longer durations of use, and associations attenuated as the latency period between aspirin assessment and lung cancer diagnosis was lengthened. Our findings, together with those from previous clinical trials and prospective studies, do not provide consistent evidence that aspirin influences the development of lung cancer and further investigation is required with adjustment for smoking. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effect of an assessment strategy using the computer decision support system (the GRAIDS software), on the management of familial cancer risk in British general practice in comparison with best current practice. The design included cluster randomised controlled trial, and involved forty-five general practice teams in East Anglia, UK. Randomised to GRAIDS (Genetic Risk Assessment on the Internet with Decision Support) support (intervention n=23) or comparison (n=22). Training in the new assessment strategy and access to the GRAIDS software (GRAIDS arm) was conducted, compared with an educational session and guidelines about managing familial breast and colorectal cancer risk (comparison) were mailed. Outcomes were measured at practice, practitioner and patient levels. The primary outcome measure, at practice level, was the proportion of referrals made to the Regional Genetics Clinic for familial breast or colorectal cancer that were consistent with referral guidelines. Other measures included practitioner confidence in managing familial cancer (GRAIDS arm only) and, in patients: cancer worry, risk perception and knowledge about familial cancer. There were more referrals to the Regional Genetics Clinic from GRAIDS than comparison practices (mean 6.2 and 3.2 referrals per 10 000 registered patients per year; mean difference 3.0 referrals; 95% confidence interval (CI) 1.2–4.8; P=0.001); referrals from GRAIDS practices were more likely to be consistent with referral guidelines (odds ratio (OR)=5.2; 95% CI 1.7–15.8, P=0.006). Patients referred from GRAIDS practices had lower cancer worry scores at the point of referral (mean difference −1.44 95% CI −2.64 to −0.23, P=0.02). There were no differences in patient knowledge about familial cancer. The intervention increased GPs' confidence in managing familial cancer. Compared with education and mailed guidelines, assessment including computer decision support increased the number and quality of referrals to the Regional Genetics Clinic for familial cancer risk, improved practitioner confidence and had no adverse psychological effects in patients. Trials are registered under N0181144343 in the UK National Research Register.British Journal of Cancer (2007) 97, 486–493. doi:10.1038/sj.bjc.6603897 www.bjcancer.com Published online 14 August 2007 [ABSTRACT FROM AUTHOR]

The aim was to assess outcome in a population-based cohort of adolescents with Hodgkin's lymphoma (HL) diagnosed in the UK's northern region over a 10-year period. Among a population of 3.09 million, 55 of 676 patients (8%) diagnosed with HL were aged 13–19. Seven had nodular lymphocyte-predominant HL, 48 classical HL (cHL). Of the latter, 36 were 16 years. Application of the Scottish and Newcastle Lymphoma Group (SNLG) prognostic index meant 21 patients were considered high risk (index 0.5). They received PVACEBOP multi-agent chemotherapy as primary therapy. Standard risk patients (SNLG index <0.5) were treated with standard ChlVPP or ABVD chemotherapy±radiotherapy. Scottish and Newcastle Lymphoma Group indexing is not valid for patients under 16. Twelve patients therefore received UKCCSG protocols (n=8), ABVD plus radiotherapy (n=2), or PVACEBOP (n=2). Forty-six patients with cHL (96%) achieved complete remission. Seven patients relapsed but all entered complete remission after salvage therapy. Five patients died: three of HL, one in an accident and one of disseminated varicella complicating cystic fibrosis. Five- and 10-year overall survival was 93 and 86%, respectively; disease-specific survival was 95 and 92%. The data suggest that older adolescents with high-risk HL require intensive protocols as primary therapy to secure optimal outcome.British Journal of Cancer (2007) 97, 29–36. doi:10.1038/sj.bjc.6603809 www.bjcancer.com Published online 29 May 2007 [ABSTRACT FROM AUTHOR]

We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86-1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86-1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14-2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer. [ABSTRACT FROM AUTHOR]

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5-10 years, 40-98% [corrected] of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals. [ABSTRACT FROM AUTHOR]

We report here the different roles undertaken by the members of 10 multidisciplinary cancer teams in conveying information to patients during their care. Team members completed an Informational Roles Questionnaire measuring an individual's perception of their major role and that of their colleagues in giving information to patients. They also completed two standard psychological health measures, the General Health Questionnaire and Maslach Burnout Inventory. The information giving roles of the surgeon, oncologist, radiologist and clinical nurse specialist were well recognised by their colleagues; however, other team members' roles were more ambiguous and less well understood. The clinical nurse specialist provided the broadest information coverage for patients. Few professional groups regularly informed patients about clinical trials and family history and the clinical nurse specialist was often the only person to deal with patients' sexual well being, consequently these areas are likely to receive poor coverage. Probable psychiatric morbidity (GHQ> or =4) in teams ranged from 5 to 27%. High levels of emotional exhaustion were particularly apparent in team leaders and nurses and feelings of low levels of personal accomplishment were prevalent in the histopathologists and radiologists. Putative benefits to patients and healthcare professionals from multidisciplinary team working may not be realised without investment in team training. [ABSTRACT FROM AUTHOR]

Mammographic screening before age 50 years is less effective than at older ages and the associated radiation risks are higher. We estimated how many breast cancer deaths could be caused and how many could be prevented by a decade of annual two-view mammographic screening starting at ages 20, 30 and 40 years, respectively, in the UK; for all women, and for women with first-degree relatives affected with breast cancer. We extrapolated from a radiation risk model to estimate the number of radiation-induced breast cancer deaths, and used results from randomised trials, which suggest a reduction in breast cancer mortality of 10–20% in women invited to screening before age 50 years, to estimate the number of deaths that could be prevented. The net change in breast cancer deaths was defined as the number of radiation-induced deaths minus the number of prevented deaths. For all women, assuming a reduction in mortality from screening of 20%, a decade of annual screening was estimated to induce more deaths than it prevents if started at age 20 years and at age 30 years (net increase=0.86 and 0.37 breast cancer deaths, respectively, per 1000 women screened). The corresponding estimate for screening starting at age 40 years was a net decrease of 0.46 deaths/1000 women screened and a zero net change assuming a 10% mortality reduction. Results for women with first-degree relatives with breast cancer were generally in the same direction but, because their background incidence rates are higher, the net increases or decreases were greater. In conclusion, our estimates suggest that a decade of annual two-view mammographic screening before age 40 years would result in a net increase in breast cancer deaths, and that starting at age 40 years could result in a material net decrease only if breast cancer mortality is reduced by about 20% or more in women screened. Although these calculations were based on a number of uncertain parameters, in general, the conclusions were not altered when these parameters were varied within a feasible range.British Journal of Cancer (2005) 93, 590–596. doi:10.1038/sj.bjc.6602683 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Comparisons of survival rates of given diseases with different treatments or in different places often gave misleading results until the introduction of controlled trials. Recent reports of relatively low survival rates following the treatment of cancer in the UK compared to the rates in other countries, not based on controlled trials, may consequently be misleading. Their validity has, therefore, been tested by comparing the levels and trends in mortality--the ultimate criterion by which the success or failure of any system of care can be judged. For this purpose, rates and trends in rates over 20-50 years have been compared in five European countries of similar economic status (France, Italy, the Netherlands, Sweden, and the UK). The UK rates are not generally worse than those in the other countries and are sometimes better. Exceptions were cancer of the lung, large bowel, and breast, the first of which is explained by differences in the prevalence of smoking. [ABSTRACT FROM AUTHOR]

We aimed to study trends in the design and conduct of randomised controlled trials (RCTs) in cancer in the UK, using the UK Coordinating Committee for Cancer Research (UKCCCR) National Register of Cancer Trials (NRCT). We conducted a descriptive survey of 520 UK RCTs in cancer that were registered on the UKCCCR NRCT. All trials had been initiated between 1971 and 2000. Trials on the NRCT have been conducted in a wide variety of cancer types, but with a third in breast (22%) or lung cancer (11%). They have largely been funded by the UK public and charity sectors. Overall, there has been a sustained rise in the total numbers of patients entering UK cancer trials over time with a trend towards larger, multicentre trials, greater recruitment targets and a marked reduction in the average time taken to complete trials. Trends in the design and conduct of noncommercial cancer RCTs from 1971 to 2000 are encouraging. It will be interesting to see how they develop in light of the implementation of recent national initiatives regarding cancer clinical trials in the UK. [ABSTRACT FROM AUTHOR]

This study estimated lifetime cost of treatment for patients in the United Kingdom (UK) presenting with stage IV breast cancer. To determine patterns of treatment and resource use in the absence of direct observational data, a cancer physician panel was surveyed. The survey questionnaire described four predefined treatment phases: active treatment; follow-up after active treatment until disease progression; active supportive care after progression; and end-of-life care. Physicians were asked their major treatment strategies for each phase. Monthly cost and average lifetime cost per patient were calculated. Only five cancer registries in the UK document the proportion of breast cancer patients diagnosed with stage IV disease. Their data was used to estimate the incidence of metastatic breast cancer at presentation throughout the UK. This value, together with lifetime cost per patient and projected survival time, allowed approximation of the overall cost for this population of cancer patients in the UK. Annual incidence of stage IV breast cancer at presentation in the UK is approximately 2100; according to treatment practice in 2002, lifetime cost per patient is pound 12 500 and total population cost is approximately pound 26 million. The substantial economic burden associated with patients diagnosed with metastatic breast cancer should be considered when developing strategies for reducing its incidence such as increased awareness, screening and preventative measures. [ABSTRACT FROM AUTHOR]

Although high-dose methotrexate (HD-MTX) is the most effective drug against primary CNS lymphomas (PCNSL), outcome-determining variables related to its administration schedule have not been defined. The impact on toxicity and outcome of the area under the curve (AUCMTX), dose intensity (DIMTX) and infusion rate (IRMTX) of MTX and plasmatic creatinine clearance (CLcrea) was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-based combinations. Anticonvulsants were administered in 31 pts (69%). Age >60 years, anticonvulsant therapy, slow IRMTX (?800?mgm-2h-1), and reduced DIMTX (?1000?mgm-2wk-1) were significantly correlated with low AUCMTX values. Seven patients (16%) experienced severe toxicity, which was independently associated with slow CLcrea. A total of 18 (40%) patients achieved complete remission after chemotherapy, which was independently associated with slow CLcrea. In all, 22 patients were alive at a median follow-up of 31 months, with a 3-year OS of 40±9%; slow CLcrea and AUCMTX >1100?µmol?hl-1 were independently associated with a better survival. Slow CLcrea and high AUCMTX are favourable outcome-determining factors in PCNSL, while slow CLcrea is significantly related to higher toxicity. AUCMTX significantly correlates with age, anticonvulsant therapy, IRMTX, and DIMTX. These findings, which seem to support the choice of an MTX dose ?3?gm-2 in a 4-6-h infusion, every 3-4 weeks, deserve to be assessed prospectively in future trials. MTX dose adjustments in patients with fast CLcrea should be investigated.British Journal of Cancer (2004) 90, 353-358. doi:10.1038/sj.bjc.6601472 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Over 6 million people around the world die from cancer each year. Modifiable risk factors have been linked to a wide range of malignancies, including cancers of the oropharynx, oesophagus, larynx, lung, kidney, bladder, pancreas, skin, stomach, ovary, breast, cervix, uterus, prostate, and colon. Research indicates that over half of all cancers in developed countries could be prevented if we implemented population-wide measures to promote the following behaviours: reduce tobacco use, increase physical activity, control weight, improve diet, limit alcohol, utilise safer sex practices, get routine cancer screening tests, and avoid excess sun exposure.British Journal of Cancer (2004) 90, 299-303. doi:10.1038/sj.bjc.6601509 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and c-myc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1?mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21-Rb-c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.British Journal of Cancer (2004) 90, 535-541. doi:10.1038/sj.bjc.6601510 www.bjcancer.com [ABSTRACT FROM AUTHOR]

TIMP-1, an ~30?kDa glycosylated protein found predominantly in extracellular compartments, is involved in the regulation of a variety of developmental, remodelling, and pathological processes. One function of TIMP-1 is to inhibit certain members of a group of extracellular and cell surface enzymes known collectively as metalloproteinases (MP). These include the matrix metalloproteinases and the adamalysin-like disintegrin and metalloproteinases (ADAMs). Additional activities of TIMP-1 include potentiating the activity of erythroid precursors and stimulating proliferation of certain cancer cell lines. Published evidence suggests that the apparent proliferative action of TIMP-1 is independent of its MP-inhibitory activity; however, reports of a cell surface receptor for TIMP-1 have not been confirmed. We have utilised a baculovirus-based system to produce TIMP-1. Data presented here show that TIMP-1 and synthetic hydroxamate (GM6001) MP inhibitors stimulate proliferation and metabolic activity of MDA-MB-435 cancer cells with similar kinetics. An inactive hydroxamate derivative was ineffective. The TIMP-1-induced increase in proliferation and metabolic activity was not the consequence of the inhibition of apoptosis by TIMP-1 in the serum-free medium. These data taken together imply that the mechanism by which TIMP-1 enhances cell growth depends on its ability to inhibit a metalloproteinase, rather than to stimulate a cell surface receptor by a process independent of its MP-inhibitory activity. Inhibitors of extracellular regulated kinase (U0126) and p38 (SB203580), and to a lesser extent the phosphatidylinositol-3-kinase inhibitor LY294002, suppressed the action of TIMP-1. Assays for ERK1/2 and p38 showed that both were activated by TIMP-1 and GM6001. Mechanisms by which TIMP-1 might act to stimulate cell proliferation are described.British Journal of Cancer (2004) 90, 463-470. doi:10.1038/sj.bjc.6601533 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P<0.001) and IBC (63%, P<0.001) was significantly greater than in normal breast (23%). There was no difference in COX-2 expression level between DCIS and IBC (P=0.87) or between normal breast from reduction mammoplasty tissue and normal breast ducts around DCIS (22%, P=0.29). In DCIS, COX-2 expression was associated with higher cellular proliferation rates (P<0.0001), nuclear grade (P=0.003), with ER negativity (P=0.003) and with HER-2 positivity (P<0.0001). Cyclooxygenase type-2 expression is upregulated in in situ breast cancer and is associated with surrogate markers of an aggressive DCIS phenotype including nonoestrogen-regulated signalling pathways. Cyclooxygenase type-2 inhibition may potentially prevent the development of ER-positive and ER-negative breast cancers.British Journal of Cancer (2004) 90, 423-429. doi:10.1038/sj.bjc.6601534 www.bjcancer.com [ABSTRACT FROM AUTHOR]

A novel nurse-delivered multicomponent intervention for major depressive disorder (MDD) in cancer outpatients was compared with usual care alone in a nonrandomised matched group design (n=30 per group). At the final 6-month outcome, 38.5% (95% CI, 5.4-57%) fewer patients in the intervention group still met the criteria for MDD.British Journal of Cancer (2004) 90, 310-313. doi:10.1038/sj.bjc.6601546 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Many cancer patients use complementary alternative medicines (CAMs) but may not be aware of the potential risks. There are no studies quantifying such risks, but there is some evidence of patient risk from case reports in the literature. A cross-sectional survey of patients attending the outpatient department at a specialist cancer centre was carried out to establish a pattern of herbal remedy or supplement use and to identify potential adverse side effects or drug interactions with conventional medicines. If potential risks were identified, a health warning was issued by a pharmacist. A total of 318 patients participated in the study. Of these, 164 (51.6%) took CAMs, and 133 different combinations were recorded. Of these, 10.4% only took herbal remedies, 42.1% only supplements and 47.6% a combination of both. In all, 18 (11.0%) reported supplements in higher than recommended doses. Health warnings were issued to 20 (12.2%) patients. Most warnings concerned echinacea in patients with lymphoma. Further warnings were issued for cod liver/fish oil, evening primrose oil, gingko, garlic, ginseng, kava kava and beta-carotene. In conclusion, medical practitioners need to be able to identify the potential risks of CAMs. Equally, patients should be encouraged to disclose their use. Also, more research is needed to quantify the actual health risks.British Journal of Cancer (2004) 90, 408-413. doi:10.1038/sj.bjc.6601560 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Ethnic differences in breast cancer survival have been observed in the USA but have not been examined in Britain. We aimed to investigate such differences between South Asian (i.e. those with family roots in the Indian subcontinent) and non-South Asian (essentially British-native) women in England. Primary breast cancer cases incident in 1986 -1993 and resident in South East England were ascertained through the Thames Cancer and Registry and followed up to the end of 1997. Cases of South Asian ethnicity were identified on the basis of their names by using a previously validated computer algorithm. A total of 1037 South Asian and 50 201 non-South Asian breast cancer cases were included in the analysis; 30% of the South Asian (n = 312) and 44% (n = 22 201) of the non-South Asian cases died during follow-up. South Asian cases had a higher relative survival than non-South Asians throughout the follow-up period. The 10-year relative survival rates were 72.6% (95% confidence interval: 69.0, 75.9%) and 65.2% (64.5, 65.8%) for South Asians and non-South Asians, respectively. The excess mortality rates experienced by South Asians were 82% (72, 94%) of those experienced by non-South Asians (P = 0.004). The magnitude of this effect was slightly reduced with adjustment for differences in age at diagnosis, but was strengthened with further adjustment for differences in stage at presentation and socioeconomic deprivation (excess mortality rates in South Asians relative to non-South Asians = 72% (63, 82%), P<0.001). These findings indicate that the higher survival from breast cancer in the first 10 years after diagnosis among South Asian was not due to differences in age at diagnosis, socioeconomic deprivation or disease stage at presentation. [ABSTRACT FROM AUTHOR]

The formation of multidisciplinary breast teams across the UK is intended to concentrate the assessment and treatment of breast cancer into the hands of high volume specialists. We undertook a retrospective population-based study in order to determine the trends in surgeon breast cancer workload in Yorkshire, UK, and to investigate whether patients treated by low-workload surgeons had poorer survival. Of 11 329 female breast cancer patients diagnosed in 1989-1994 in Yorkshire, 6% were managed by surgeons with a mean annual workload of less than 10 new patients, while surgeons with workloads of 10-29, 30-49 and >50 treated 21, 21 and 52%, respectively. Over the study period, increasing number of patients were managed by surgeons with higher workloads. Patients treated by low-workload surgeons had poorer survival. Five-year survival was 60% in the lowest workload category compared to 68% in the highest category. The relative risk of death was increased by 15% (RR =1.15, 95% CI 1.03-1.28) and by 10% (RR =1.10, 95% CI 1.02-1.18) for patients managed by surgeons with workloads <10 and 10-29 cases per annum in comparison to patients managed by surgeons with workloads of 450. The results of this study suggest increasing site specialization in breast cancer among general surgeons. It also provides further evidence that the management of patients by surgeons with low workloads decreases overall survival. [ABSTRACT FROM AUTHOR]

This study examined attitudes to human papillomavirus (HPV) testing among a purposively selected sample of women from four ethnic groups: white British, African Caribbean, Pakistani and Indian. The design was qualitative, using focus group discussion to elicit women's attitudes towards HPV testing in the context of cervical cancer prevention. The findings indicate that although some women welcomed the possible introduction of HPV testing, they were not fully aware of the sexually transmitted nature of cervical cancer and expressed anxiety, confusion and stigma about HPV as a sexually transmitted infection. The term 'wart virus', often used by medical professionals to describe high-risk HPV to women, appeared to exacerbate stigma and confusion. Testing positive for HPV raised concerns about women's sexual relationships in terms of trust, fidelity, blame and protection, particularly for women in long-term monogamous relationships. Participation in HPV testing also had the potential to communicate messages of distrust, infidelity and promiscuity to women's partners, family and community. Concern about the current lack of available information about HPV was clearly expressed and public education about HPV was seen as necessary for the whole community, not only women. The management of HPV within cervical screening raises important questions about informed participation. Our findings suggest that HPV testing has the potential to cause psychosocial harm to women and their partners and families. [ABSTRACT FROM AUTHOR]

About 6000 women in the United Kingdom develop ovarian cancer each year and about two-thirds of the women will die from the disease. Establishing the prognosis of a woman with ovarian cancer is an important part of her evaluation and treatment. Prognostic models and indices in ovarian cancer should be developed using large databases and, ideally, with complete information on both prognostic indicators and long-term outcome. We developed a prognostic model using Cox regression and multiple imputation from 1189 primary cases of epithelial ovarian cancer (with median follow-up of 4.6 years). We found that the significant (P ≤ 0.05) prognostic factors for overall survival were age at diagnosis, FIGO stage, grade of tumour, histology (mixed mesodermal, clear cell and endometrioid versus serous papillary), the presence or absence of ascites, albumin, alkaline phosphatase, performance status on the ZUBROD-ECOG-WHO scale, and debulking of the tumour. This model is consistent with other models in the ovarian cancer literature; it has better predictive ability and, after simplification and validation, could be used in clinical practice. [ABSTRACT FROM AUTHOR]

The objective was to describe NHS cancer genetic counselling services and compare UK regions. The study design was a cross-sectional study over 4 weeks and attendee survey. The setting was 22 of the 24 regional cancer genetics services in the UK NHS. Participants were individuals aged over 18 attending clinics at these services. Outcome measures were staff levels, referral rates, consultation rates, follow-up plans, waiting time. There were only 11 dedicated cancer geneticists across the 22 centres. Referrals were mainly concerned with breast (63%), bowel (18%) and ovarian (12%) cancers. Only 7% of referrals were for men and 3% were for individuals from ethnic minorities. Referral rates varied from 76 to 410 per million per annum across the regions. Median waiting time for an initial appointment was 19 weeks, ranging across regions from 4 to 53 weeks. Individuals at population-level genetic risk accounted for 27% of consultations (range 0%, 58%). Shortfalls in cancer genetics staff and in the provision of genetic testing and cancer surveillance have resulted in large regional variations in access to care. Initiatives to disseminate referral and management guidelines to cancer units and primary care should be adequately resourced so that clinical genetics teams can focus on the genetic testing and management of high-risk families. [ABSTRACT FROM AUTHOR]

Cancer incidence in 1990-92 among English south Asian (residents with ethnic origins in India, Pakistan or Bangladesh) and non-south Asian children is compared. Standardized incidence ratios show significant overall excesses in south Asians (131), largely due to higher rates in south Asian boys, and specific excesses for leukaemia (141), lymphoid leukaemia (141), lymphoma (172) and hepatic tumours (375). Aetiological investigation is required. [ABSTRACT FROM AUTHOR]

In the United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of England, Scotland and Wales, measured power-frequency magnetic fields were not found to be associated with risk for any malignancy. To examine further the risk associated with residential proximity to electricity supply equipment, distances to high-voltage lines, underground cables, substations and distribution circuits were collected for 3380 cases and 3390 controls. Magnetic field exposure from this equipment was calculated using distance, load and other circuit information. There was no evidence that either proximity to electrical installations or the magnetic field levels they produce in the UK is associated with increased risk of childhood leukaemia or any other cancer. Odds ratios of 0.73 (95% CI = 0.42-1.26) for acute lymphoblastic leukaemia, 0.75 (95% CI = 0.45-1.25) for all leukaemias, 1.08 (95% CI = 0.56-2.09) for central nervous system cancers and 0.92 (95% CI = 0.64-1.34) for all malignancies were obtained for residence within 50 m of an overhead line. When individuals with a calculated magnetic field exposure ≥ 0.2 μT were compared to those in a reference category of exposure <0.1 μT, odds ratios of 0.51 (95% CI = 0.11-2.33) for acute lymphoblastic leukaemia, 0.41 (95% CI = 0.09-1.87) for total leukaemia, 0.48 (95% CI =0.06-3.76) for central nervous system cancers and 0.62 (95% CI = 0.24-1.61) for all malignancies were obtained. [ABSTRACT FROM AUTHOR]

Evidence suggests wide variation in cancer care between different hospitals in the UK. To establish bench-marking data, we designed a prospective, 1 year regional study comparing key performance measures with established standards for the 28 hospital Trusts in the South and West of England involved in head and neck cancer care. 566 sequential patients with a newly-diagnosed head and neck cancer were included. Numbers referred and treated per hospital Trust were 1-58 and 1-65 respectively. 59% of patients received a pretreatment chest X-ray (standard 95%). 45% of patients were seen in a multidisciplinary clinic pretreatment (standard 95%), and this was proportional to the frequency of clinics held (P < 0.0001). Median number of cases treated per surgeon was 4 (1-26), and by radiotherapist was 10 (1-51). Times between parts of the process of oral cancer care were closer to the standards than those for laryngeal cancer. Two patients were entered into a clinical trial. One had a quality-of-life score. Thus, in 1996-1997, in the South and West of England, there were major discrepancies between actual performance and established standards in many fundamental aspects of head and neck cancer care. Re-audit is essential to determine if the implementation of the Calman-Hine report has resulted in improvements. [ABSTRACT FROM AUTHOR]

The feasibility of targeted screening for cutaneous malignant melanoma in the UK using a postal questionnaire and invitation to screening by a consultant dermatologist was investigated in a population based cross-sectional survey. A total of 1600 people aged 25-69 years, stratified by the social deprivation score of wards within one general practice, were randomly selected from a population of 8000.1227 (77%) returned the questionnaire and 896 (56%) attended the screening clinic. Uptake was lower for men (P < 0.001), those aged under 50 (P < 0.001), people from deprived areas (P < 0.001) and skin types III and IV (men only, P < 0.001). Twenty per cent of women and 10% of men felt nervous about attending the clinic, but only 4% were worried by the questionnaire. The level of agreement between the self- and dermatologist's assessments of risk factors was best for hair colour (Kappa = 0.67, sensitivity 73% and specificity 98%). People tended to under-report their level of risk. Over 95% knew about at least one major sign, but 54% reported incorrect signs of melanoma. Targeted screening for melanoma in the UK will be hampered by difficulties in accurately identifying the target population. Strategies to improve skin self-awareness rather than screening should be developed and evaluated. [ABSTRACT FROM AUTHOR]

Survival following cancer was analysed in relation to ethnic group among children diagnosed in Britain during 1981-1996 and treated at paediatric oncology centres by members of the UK Children's Cancer Study Group. Survival was analysed for 11 diagnostic groups: acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, astrocytoma, primitive neuroectodermal tumour, neuroblastoma, Wilms' tumour, osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. There were no significant differences in survival between White and non-White children over the study period as a whole. Among children with ALL, however, the relative risk of death allowing for period of diagnosis, age and white blood count was 1.25 for those of South Asian ethnic origin compared with Whites (P = 0.057). [ABSTRACT FROM AUTHOR]

A UK population-based case-control study of Hodgkin's disease (HD) in young adults (16-24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein-Barr virus (EBV) status (EBV present in Reed-Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10-5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07-78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for > or =2 episodes compared with < or =1, OR = 0.45, 95% CI = 0.25-0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study. [ABSTRACT FROM AUTHOR]

Background: The prognosis of non-Hodgkin lymphoma and Hodgkin lymphoma is not affected by HIV serostatus, yet people living with HIV (PLWH) are frequently excluded from clinical trials in lymphoma.Methods: The UK NIHR Clinical Research Network Study Portfolio website was used to identify all the open clinical trials in lymphoma in the United Kingdom in January 2015. Trials that excluded PLWH were further investigated to evaluate if the exclusion was justified by scientific evidence.Results: We identified 56 multicentre open clinical trials in lymphoma including 46 interventional trials. People living with HIV were excluded from 32 interventional trials (70%). We identified a biologically valid reason (a potential increased risk of greater immunosuppression) for excluding PLWH from one trial and possibly for one optional arm in another study.Conclusions: There was no scientific or safety justification for excluding PLWH from most lymphoma clinical trials included on the NIHR portfolio. A clear justification for excluding PLWH was not offered in the available protocols. The exclusion of PLWH should be explicitly justified on scientific grounds in protocols to minimise stigmatisation. [ABSTRACT FROM AUTHOR]

Presents information regarding various congresses and conventions held in the field of medicine in Great Britain as of 1999. Date for the Micro 2000 International Microscopy Exhibition and Conference in London, England; Venue and date for a meeting of the Section of Urology, Royal Society of Medicine and the British Prostrate Group; Convention on radiology in Birmingham, England.

The mortality of all 14 319 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1992, and cancer incidence was examined from 1971 to 1986, in relation to their exposures to plutonium and to external radiation. The cancer mortality rate was 5% lower than that of England and Wales and 3% less than that of Cumbria. The significant excesses of deaths from cancer of the pleura and thyroid found in an earlier study persist with further follow-up (14 observed, 4.0 expected for pleura; 6 observed, 2.2 expected for thyroid). All of the deaths from pleural cancer were among radiation workers. For neither site was there a significant association between the risk of the cancer and accumulated radiation dose. There were significant deficits of deaths from cancers of mouth and pharynx, liver and gall bladder, and larynx and leukaemia when compared with the national rates. Among all radiation workers, there was a significant positive association between accumulated external radiation dose and mortality from cancers of ill-defined and secondary sites (10-year lag,P = 0.04), leukaemia (no lag,P = 0.03; 2-year lag,P = 0.05), multiple myeloma (20-year lag,P = 0.02), all lymphatic and haematopoietic cancers (20-year lag,P = 0.03) and all causes of death combined (20-year lag,P = 0.008). Among plutonium workers, there were significant excesses of deaths from cancer of the breast (6 observed, 2.6 expected) and ill-defined and secondary cancers (29 observed, 20.1 expected). No significant positive trends were observed between the risk of deaths from cancers of any specific site, or all cancers combined, and cumulative plutonium and external radiation doses. For no cancer site was there a significant excess of cancer registrations compared with rates for England and Wales. Analysis of trends in cancer incidence showed significant increases in risk with cumulative plutonium plus external radiation doses for all lymphatic... [ABSTRACT FROM AUTHOR]

Background:The prognosis for hepatocellular carcinoma (HCC) is dependent upon tumour stage, performance status (PS), severity of underlying liver disease, and the availability of appropriate therapies. The unavailability of sorafenib may have a significantly adverse effect on the prognosis of UK patients with advanced HCC. During the study period, access to sorafenib was at the discretion of local health funding bodies, a process that may delay or deny access to the drug and that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt to address the impact of this system on patients with advanced HCC in the United Kingdom.Methods:This is a retrospective study performed in the two largest specialist hepatobiliary oncology units in the United Kingdom. Funding applications were made to local funding bodies for patients with advanced HCC for whom sorafenib was considered appropriate (advanced HCC not suitable for loco-regional therapies, compensated chronic liver disease, PS 0-2).Results:A total of 133 applications were made, of which 57 (43%) were approved and 76 (57%) declined. Demographics and prognostic factors were balanced between the two groups. This cohort had a number of adverse prognostic features: patients were predominantly PS 1-2; the majority had multifocal disease with the largest lesion being >5 cm; and macroscopic vascular invasion, metastases, and AFP >1000 ng ml−1, were each present in one-third of cases. The median time from application to funding decision was 17 days (range 3-260 days). For the primary 'intention-to-treat' analysis, median overall survival was 4.1 months when funding was declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95% CI 0.3186-0.7267; P=0.0005).Conclusion:These data support the use of sorafenib for patients with advanced HCC as an effective intervention. In the United Kingdom, this applies to a relatively small group of patients, estimated to total ∼800 per year who, unfortunately, do not survive long enough to themselves lobby for the availability of this drug. These data provide a comparison of sorafenib with supportive care and demonstrate the potential detrimental impact on patient outcomes of rationing health-care resources on the basis of cost. [ABSTRACT FROM AUTHOR]

We investigated prostate cancer incidence in East Anglia from 1971 to 2000. Using age-period-cohort modelling, the number of cases expected in 1991-2000, based on pre-PSA trends, 1971-1990, was compared with that observed. Based on pre-1991 trends, 9203 new cases were expected in 1991-2000, but 9788 cases were observed, an excess of 6%. [ABSTRACT FROM AUTHOR]