Regional melanoma incidence in England, 1996-2006: reversal of north-south latitude trends among the young female population.

BACKGROUND: Melanoma incidence often shows an increasing latitudinal gradient from north to south among white European populations. OBJECTIVES: To assess emerging regional melanoma incidence patterns in England. METHODS: All primary invasive cutaneous melanomas diagnosed in England in people aged 10-89 years, in 1996-2006, were ascertained. Age-standardized incidence rates by sex, age and Government Office Region were calculated for the entire population and for the white population only. Rates according to socioeconomic deprivation were further calculated among those aged under 30 years. Regional heterogeneity and latitude and deprivation trends were assessed by Poisson regression and tests for trend. RESULTS: Overall, melanoma incidence in England was highest in the South West (overall, 18·75; white, 19·03 per 100,000) and lowest in London (overall, 8·85; white, 11·22 per 100,000). Incidence significantly increased with more southerly latitudes in all white adults aged over 30 years (P < 0·0001), except women aged 30-49 years (1·8%, P = 0·10). However, these north-south latitude trends were reversed in white 10-29 year olds, with sex-specific analyses showing an absence of trend in male subjects (2·7%, P = 0·41) and a strong decreasing trend (-9·8%, P < 0·0001) in female subjects. The highest rates in the young female population occurred in the North West (5·46 per 100,000), and specifically in the second most deprived (5·69 per 100,000) and the second most affluent (6·48 per 100,000) groups. CONCLUSIONS: Melanoma incidence is high in young people in northern England, including among the moderately deprived, reversing the expected north-south incidence gradients. Prevalent sunbed use in northern England and holiday sun exposure abroad may explain these emerging trends.

Increases in invasive melanoma in England, 1979-2006, by anatomical site.

BACKGROUND: National melanoma incidence trends with details of anatomical site have not been previously described for England. OBJECTIVES: To describe site-specific trends in cutaneous melanoma for England as a whole during the last three decades. METHODS: Anonymized data, 1979-2006, were obtained from national cancer registrations of all patients in England up to age 89years with incident primary invasive cutaneous melanomas (n=124055). Sex-specific age-standardized incidence rates and average annual percentage change in rates were calculated for each broad anatomical site. RESULTS: Overall incidence rates of cutaneous melanoma in England, 1979-2006, were 81 and 100 per million, in males and females, respectively. Site-specific rates were consistently highest on the lower limbs in females followed by the trunk in males. Greatest annual increases occurred on the trunk in both sexes over 45years (males 9·9%, females 6·8%), then upper limbs (males 8·7%, females 6·8%). Incidence trends in males relative to females varied little across sites apart from a more rapid rise in head/neck melanomas in males than in females after the 1980s. CONCLUSIONS: Invasive melanoma rates continue to rise in England, particularly on the trunk and arms, and in males on the head/neck. The steeper increases in melanoma rates among males are consistent with their greater sun exposure and poorer compliance with sun protection measures than females.

Geographical and temporal distribution of cancer survival in teenagers and young adults in England.

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.

Survival from cancer in teenagers and young adults in England, 1979-2003.

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13-24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30,000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996-2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.

Cancer mortality in 13 to 29-year-olds in England and Wales, 1981-2005.

We examined cancer mortality at ages 13-29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkin's lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval -2.09 to -1.62). Cancer groups with the highest mortality differed from those with the highest incidence.

Cancer incidence patterns by region and socioeconomic deprivation in teenagers and young adults in England.

Data on 35,291 individuals with cancer, aged 13-24 years, in England from 1979 to 2001 were analysed by region and socio-economic deprivation of census ward of residence, as measured by the Townsend deprivation index. The incidence of leukaemia, lymphoma, central nervous system tumours, soft tissue sarcomas, gonadal germ cell tumours, melanoma and carcinomas varied by region (P<0.01, all groups) but bone tumour incidence did not. Lymphomas, central nervous system tumours and gonadal germ cell tumours all had higher incidence in less deprived census wards (P<0.01), while chronic myeloid leukaemia and carcinoma of the cervix had higher incidence in more deprived wards (P<0.01). In the least deprived wards, melanoma incidence was nearly twice that in the most deprived, but this trend varied between regions (P<0.001). These cancer incidence patterns differ from those seen in both children and older adults and have implications for aetiology and prevention.

Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of pathological Langerhans cells, for which the aetiology and pathogenesis remain largely unknown. PROCEDURE: Information on the 101 children with LCH registered with the population-based Manchester Children's Tumour Registry (MCTR) between 1954 and 1998 was extracted from the records of the MCTR. This included age, sex, date of diagnosis, systems affected at diagnosis and follow-up. RESULTS: The overall incidence rate for LCH was 2.6 cases per million child years. In those under 1 year of age the incidence rate was 9.0 cases per million child years, compared to 0.7 cases per million in those aged 10-14 years (P < 0.0001 for age trend). There was no evidence of seasonal variation in presentation by month of birth or first symptom. Bone was the most common site of disease involvement (67% of cases), followed by skin (37%) and soft tissue (22%). The overall survival rate has improved over time, from 57% in 1954-1968 to 74% in 1985-1998. Ninety percent of deaths were due to disease progression, the remainder were due to complications of intensive therapy. The site of LCH lesions and extent of disease present at diagnosis strongly predicted survival outcome. Patients with initial liver involvement had a 5-year survival rate of 25% compared with 93% for those with bone lesions alone at diagnosis. CONCLUSIONS: Incidence rates varied significantly by age at diagnosis, and have been stable over time. Survival has improved considerably over time, but varies strongly by age and systems affected at diagnosis.

Incidence of malignant disease by morphological type, in young persons aged 12-24 years in England, 1979-1997.

Cancer incidence data are generally presented in terms of primary site, but this method is inappropriate for cancers in young persons. We have used a morphology-based classification system to produce national incidence rates for cancers in persons aged 12-24 years by detailed diagnostic sub-type. The overall incidence rates for malignant disease in young persons aged 12-14, 15-19 and 20-24 years were 10.1, 14.4 and 22.6 per 100000 population, respectively. The three most frequent cancer types in 12-14-year-olds were leukaemias, lymphomas and central nervous system (CNS) tumours. In 15-19-year-olds, lymphomas were most frequent and leukaemias second with carcinomas third. In 20-24-year-olds, lymphomas were again most frequent, but carcinomas and germ cell tumours were second and third. There was also variation with age in the ratios of rates in males and females. These changing incidence patterns have aetiological implications and provide clues for future hypothesis-based research.

Childhood medulloblastoma in northwest England 1954 to 1997: incidence and survival.

The incidence, survival patterns, and presenting symptoms of children with medulloblastoma were studied. Data were ascertained from the Manchester Tumour Registry which is population-based and has collected data on all childhood malignancies in northwest England since 1954. Incidence rates standardized to the European standard population were calculated and Poisson regression models were used to examine temporal changes in the incidence rates during the period 1954 to 1997. Kaplan-Meier survival curves were derived and used to study changes in survival patterns. World-standardized incidence rates were 5.5 per million child years in males and 3.4 per million child years in females. Incidence rates increased from the 1950s to the 1980s but have declined recently. The 5-year survival rate has improved from 29 to 58% with similar rates for males and females. The 1-year survival rate has also improved, but females had worse survival at this point (58%) than males (75%). The type of symptom or sign at presentation is strongly affected by age, with 10 of the 22 recorded symptoms or signs showing significant age differences. The older the child is, the more likely is the presentation to show pressure features of headache, vomiting, and ophthalmic signs. Younger children present with non-specific features such as lethargy, behavioural disturbance, or increasing head size. Ataxia is seen in about 75% of children across the age range.

Classification and incidence of cancers in adolescents and young adults in England 1979-1997.

Cancer patients aged 15-24 years have distinct special needs. High quality cancer statistics are required for service planning. Data presented by primary site are inappropriate for this age group. We have developed a morphology-based classification and applied it to national cancer registration data for England 1979-1997. The study included 25,000 cancers and 134 million person-years at risk. Rates for each diagnostic group by age, sex and time period (1979-83, 1984-87, 1988-92, 1993-1997) were calculated. Overall rates in 15-19 and 20-24-year-olds were 144 and 226 per million person-years respectively. Lymphomas showed the highest rates in both age groups. Rates for leukaemias and bone tumours were lower in 20-24 year olds. Higher rates for carcinomas, central nervous system tumours, germ-cell tumours, soft tissue sarcomas and melanoma were seen in the older group. Poisson regression showed incidence increased over the study period by an average of 1.5% per annum (P<0.0001). Significant increases were seen in non-Hodgkins lymphoma (2.3%), astrocytoma (2.3%), germ-cell tumours (2.3%), melanoma (5.1%) and carcinoma of the thyroid (3.5%) and ovary (3.0%). Cancers common in the elderly are uncommon in adolescents and young adults. The incidence of certain cancers in the latter is increasing. Future studies should be directed towards aetiology.

Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants.

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.

Relative frequency and morphology of cancers in carriers of germline TP53 mutations.

The spectrum and frequency of cancers associated with germline TP53 mutations are uncertain. To address this issue a cohort of individuals from 28 families with Li-Fraumeni syndrome, segregating germline TP53 mutations was established. Predicted cancers were estimated by applying age, morphology, site and sex-specific UK cancer statistics to person-years at risk. Observed and predicted cancers were compared and two-sided P-values calculated. Cancer types occurring to excess and showing P-values <0.02, were designated strongly associated with germline TP53 mutations. These were removed from the data and a second round of analyses performed. Cancer types with P-values <0.02 and 0.02-0.05 in the second round analyses were considered moderately and weakly associated respectively. Strongly associated cancers were: breast carcinoma, soft tissue sarcomas, osteosarcoma, brain tumours, adrenocortical carcinoma, Wilms' tumour and phyllodes tumour. Carcinoma of pancreas was moderately associated. Leukaemia and neuroblastoma were weakly associated. Other common carcinomas including lung, colon, bladder, prostate, cervix and ovary did not occur to excess. Although breast carcinoma and sarcomas were numerically most frequent, the greatest increases relative to general population rates were in adrenocortical carcinoma and phyllodes tumour. We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects.

Fitting host-parasitoid models with CV2 > 1 using hierarchical generalized linear models.

The powerful general Pacala-Hassell host-parasitoid model for a patchy environment, which allows host density-dependent heterogeneity (HDD) to be distinguished from between-patch, host density-independent heterogeneity (HDI), is reformulated within the class of the generalized linear model (GLM) family. This improves accessibility through the provision of general software within well-known statistical systems, and allows a rich variety of models to be formulated. Covariates such as age class, host density and abiotic factors may be included easily. For the case where there is no HDI, the formulation is a simple GLM. When there is HDI in addition to HDD, the formulation is a hierarchical generalized linear model. Two forms of HDI model are considered, both with between-patch variability: one has binomial variation within patches and one has extra-binomial, overdispersed variation within patches. Examples are given demonstrating parameter estimation with standard errors, and hypothesis testing. For one example given, the extra-binomial component of the HDI heterogeneity in parasitism is itself shown to be strongly density dependent.