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1.  DNA methylation gene-based models indicating independent poor outcome in prostate cancer 
BMC Cancer  2014;14(1):655.
Background
Prostate cancer has a variable clinical behaviour with frequently unpredictable outcome. DNA methylation plays an important role in determining the biology of cancer but prognostic information is scanty. We assessed the potential of gene-specific DNA methylation changes to predict death from prostate cancer in a cohort of untreated men in the UK.
Methods
This was a population-based study in which cases were identified from six cancer registries in Great Britain. DNA was extracted from formalin-fixed paraffin wax-embedded transurethral prostate resection tissues collected during 1990-96 from men with clinically-localised cancer who chose not to be treated for at least 6 months following diagnosis. The primary end point was death from prostate cancer. Outcomes were determined through medical records and cancer registry records. Pyrosequencing was used to quantify methylation in 13 candidate genes with established or suggested roles in cancer. Univariate and multivariate Cox models were used to identify possible predictors for prostate cancer-related death.
Results
Of 367 men, 99 died from prostate cancer during a median of 9.5 years follow-up (max = 20). Univariately, 12 genes were significantly associated with prostate cancer mortality, hazard ratios ranged between 1.09 and 1.28 per decile increase in methylation. Stepwise Cox regression modelling suggested that the methylation of genes HSPB1, CCND2 and DPYS contributed objective prognostic information to Gleason score and PSA with respect to cancer-related death during follow-up (p = 0.006).
Conclusion
Methylation of 13 genes was analysed in 367 men with localised prostate cancer who were conservatively treated and stratified with respect to death from prostate cancer and those who survived or died of other causes. Of the 13 genes analysed, differential methylation of HSPB1, CCND2 and DPYS provided independent prognostic information. Assessment of gene-methylation may provide independent objective information that can be used to segregate prostate cancers at diagnosis into predicted behavioural groups.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-655) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-655
PMCID: PMC4162944  PMID: 25193387
DNA methylation; Prostate cancer; Progression biomarkers; Watchful waiting; Pyrosequencing
2.  Incidence and survival of oesophageal and gastric cancer in England between 1998 and 2007, a population-based study 
BMC Cancer  2012;12:11.
Background
Major changes in the incidence of oesophageal and gastric cancers have been reported internationally. This study describes recent trends in incidence and survival of subgroups of oesophageal and gastric cancer in England between 1998 and 2007 and considers the implications for cancer services and policy.
Methods
Data on 133,804 English patients diagnosed with oesophageal and gastric cancer between 1998 and 2007 were extracted from the National Cancer Data Repository. Using information on anatomical site and tumour morphology, data were divided into six groups; upper and middle oesophagus, lower oesophagus, oesophagus with an unspecified anatomical site, cardia, non-cardia stomach, and stomach with an unspecified anatomical site. Age-standardised incidence rates (per 100,000 European standard population) were calculated for each group by year of diagnosis and by socioeconomic deprivation. Survival was estimated using the Kaplan-Meier method.
Results
The majority of oesophageal cancers were in the lower third of the oesophagus (58%). Stomach with an unspecified anatomical site was the largest gastric cancer group (53%). The incidence of lower oesophageal cancer increased between 1998 and 2002 and remained stable thereafter. The incidence of cancer of the cardia, non-cardia stomach, and stomach with an unspecified anatomical site declined over the 10 year period. Both lower oesophageal and cardia cancers had a much higher incidence in males compared with females (M:F 4:1). The incidence was also higher in the most deprived quintiles for all six cancer groups. Survival was poor in all sub-groups with 1 year survival ranging from 14.8-40.8% and 5 year survival ranging from 3.7-15.6%.
Conclusions
An increased focus on prevention and early diagnosis, especially in deprived areas and in males, is required to improve outcomes for these cancers. Improved recording of tumour site, stage and morphology and the evaluation of focused early diagnosis programmes are also needed. The poor long-term survival reinforces the need for early detection and multidisciplinary care.
doi:10.1186/1471-2407-12-11
PMCID: PMC3274437  PMID: 22239958
3.  Trends in the incidence and survival of multiple myeloma in South East England 1985-2004 
BMC Cancer  2010;10:74.
Background
Multiple myeloma is an uncommon cancer with a poor prognosis. Its incidence is expected to increase due to ageing populations and better diagnosis, and new treatments have been developed to improve survival. Our objective was to investigate trends in the epidemiology and survival of multiple myeloma for South East England.
Methods
Data on 15,010 patients diagnosed with multiple myeloma between 1985 and 2004 was extracted from the Thames Cancer Registry database. We calculated the yearly age-standardised incidence rates for males and females and age-specific incidence rates in 10-year age groups for both sexes combined. We also explored geographical variation in incidence across primary care trusts. We then used period analysis to calculate trends in 1- and 5-year relative survival over the 15 years 1990-2004, comparing survival by sex and by age group 59 years and below versus 60 years and above. Finally, we investigated 5-year relative survival for the period 2000-2004 by socio-economic deprivation, assigning patients to quintiles of deprivation using the Income Domain of the Index of Multiple Deprivation 2004 based on postcode of residence.
Results
The incidence of multiple myeloma was higher in males than in females and in patients over 70, throughout the period 1985-2004. No obvious geographical pattern of incidence by primary care trust emerged. The 1- and 5-year relative survival of male and female patients increased in both age groups and was statistically significant in males aged over 60. There was a tendency for better survival in patients resident in the most affluent areas, but this did not reach statistical significance.
Conclusions
The trends in incidence of multiple myeloma in males and females are similar to that reported from other western populations. Relative survival was higher for younger patients although we found significant improvements in 1-year relative survival for male patients over 60 years old. The improved survival demonstrated for patients of all ages is likely to reflect increased detection, earlier diagnosis and the introduction of new treatments. Future studies should investigate the influence of ethnicity on incidence and survival, and the effect of specific treatments on survival and quality of life.
doi:10.1186/1471-2407-10-74
PMCID: PMC2837016  PMID: 20193064
4.  Certified causes of death in patients with mesothelioma in South East England 
BMC Cancer  2009;9:28.
Background
Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence.
Methods
We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1) mesothelioma deaths, (2) deaths certified as lung cancer deaths or (3) deaths from unspecified cancer, and (4) deaths from other causes.
Results
87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate.
Conclusion
This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.
doi:10.1186/1471-2407-9-28
PMCID: PMC2639607  PMID: 19166594
5.  Variation in incidence of breast, lung and cervical cancer and malignant melanoma of skin by socioeconomic group in England 
BMC Cancer  2008;8:271.
Background
Cancer incidence varies by socioeconomic group and these variations have been linked with environmental and lifestyle factors, differences in access to health care and health seeking behaviour. Socioeconomic variations in cancer incidence by region and age are less clearly understood but they are crucial for targeting prevention measures and health care commissioning.
Methods
Data were obtained from all eight English cancer registries for patients diagnosed between 1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50), lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was assigned to each patient based on their postcode of residence at diagnosis, using the income domain of the Index of Multiple Deprivation 2004. We analysed the socioeconomic variations in the incidence of breast, lung and cervical cancer and malignant melanoma of the skin for England, and regionally and by age.
Results
Incidence was highest for the most deprived patients for lung cancer and cervical cancer, whilst the opposite was observed for malignant melanoma and breast cancer. The difference in incidence between the most and the least deprived groups was higher for lung cancer patients aged under 65 at diagnosis than those over 65 at diagnosis, which may indicate a cohort effect. There were regional differences in the socioeconomic gradients with the gap being widest for lung and cervical cancer in the North (North East, North West and Yorkshire and Humberside) and for malignant melanoma in the East and South West. There were only modest variations in breast cancer incidence by region. If the incidence of lung and cervical cancer were decreased to that of the least deprived group it would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was highest in the least deprived group, therefore if all socioeconomic groups had incidence rates similar to the least deprived group it is estimated that the number of cases would increase by 7% for breast cancer, 27% for melanoma in men and 29% for melanoma in women.
Conclusion
National comparison of socioeconomic variations in cancer incidence by region and age can provide an unbiased basis for public health prevention and health commissioning. Decreasing inequalities in incidence requires the integration of information on risk factors, incidence and projected incidence but targeted public health interventions could help to reduce regional inequalities in incidence and reduce the future cancer burden.
doi:10.1186/1471-2407-8-271
PMCID: PMC2577116  PMID: 18822122
6.  Histological subtype of lung cancer in relation to socio-economic deprivation in South East England 
BMC Cancer  2008;8:139.
Background
Previous studies have found differences in the histological subtypes of lung cancers affecting males and females. Our objective was to investigate trends in the incidence of histological subtypes of lung cancer in males and females in relation to socio-economic deprivation in South East England.
Methods
Data on 48,031 males and 30,454 females diagnosed with lung cancer between 1995 and 2004 were extracted from the Thames Cancer Registry database. Age-standardised incidence rates for histological subtypes were calculated for each year, using the European standard population. Using the Income Domain of the Multiple Index of Deprivation 2004, patients diagnosed between 2000 and 2004 were classified into quintiles of socio-economic deprivation based on their postcode of residence. Age-standardised rates for each histological subtype were then calculated for each deprivation quintile. A Poisson regression model was fitted to the data for males and females separately to test the hypothesis that the relationship between socio-economic deprivation and adenocarcinoma was less strong than for other subtypes.
Results
In males all specific histological subtypes except adenocarcinoma declined in incidence. Squamous cell carcinoma remained the most common specific subtype and large cell carcinoma the least common. In females squamous cell carcinoma was initially most common, but its incidence declined slightly and that for adenocarcinoma increased. In both sexes the overall age-standardised incidence rate of lung cancer increased with increasing deprivation. However, these trends were less strong for adenocarcinoma than for the other subtypes in both males (p < 0.001) and females (p = 0.003).
Conclusion
The temporal trends and distribution of histological subtypes of lung cancer in males and females are similar to that reported from other western populations. In both males and females, adenocarcinoma was less strongly related to deprivation than other subtypes. This may be because its development is less strongly linked to individual smoking history.
doi:10.1186/1471-2407-8-139
PMCID: PMC2416361  PMID: 18489782
7.  Radiotherapy waiting times for women with breast cancer: a population-based cohort study 
BMC Cancer  2007;7:71.
Background
Waiting times for cancer patients are a national priority in the UK. Previous studies have shown variation between cancer networks in the time between diagnosis and start of radiotherapy for all cancer patients. Studies of the relationship between delay in receiving treatment and survival of breast cancer patients have been inconsistent. This study aimed to examine factors associated with waiting times for radiotherapy for breast cancer patients.
Methods
35,354 women resident in South East England and diagnosed with breast cancer between 1992 and 2001 who received radiotherapy within six months of diagnosis were identified from the Thames Cancer Registry. Time to radiotherapy was measured from either the date of diagnosis or the start of the previous treatment, whichever was shorter. Unadjusted and adjusted logistic regression models were fitted to examine whether patients received radiotherapy within 60 days of their diagnosis or previous treatment.
Results
The adjusted proportions of patients receiving radiotherapy within 60 days varied significantly between different cancer networks (range: 43% to 81%), and decreased from 68% in 1992 to 33% in 2001. After adjustment there was no association between deprivation of area of residence, age or stage and radiotherapy wait. Median time waited to radiotherapy increased over the study period whether measured from the start of chemotherapy, hormone therapy, surgery or the date of diagnosis.
Conclusion
This study covered a period of time before the investment following the Cancer Plan of 2000. Results are consistent with other findings suggesting variation between cancer networks and increasing waits over time. Further studies should examine different methods of measuring waiting time, the causes and consequences of waits for radiotherapy and the effect of current initiatives and investments.
doi:10.1186/1471-2407-7-71
PMCID: PMC1868745  PMID: 17472746
8.  Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study 
BMC Cancer  2007;7:9.
Background
Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right.
Methods
All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis.
Results
A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014).
Conclusion
We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in cardiovascular mortality induced by radiotherapy may be substantial, as these mortality events are relatively common.
doi:10.1186/1471-2407-7-9
PMCID: PMC1784099  PMID: 17224064

Results 1-8 (8)