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BackgroundMelanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops.ObjectivesWe examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk.MethodsWe analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls.ResultsWhen cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity&nbsp

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients’ risk. Objectives: To develop and validate a model for incident first‐primary cutaneous melanoma using clinically assessed risk factors. Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.

Vitamin D may reduce mortality from prostate cancer (PC). We examined the associations of post-treatment plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with PC mortality. Participants were PC cases from the New South Wales Prostate Cancer Care. All contactable and consenting participants, at 4.9 to 8.6 years after diagnosis, were interviewed and had plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) measured in blood specimens. Cox regression allowing for left-truncation was used to calculate adjusted mortality hazards ratios (HR) and 95% confidence intervals (95% CI) for all-cause and PC-specific mortality in relation to vitamin D levels and other potentially-predictive variables. Of the participants (n = 111; 75·9% response rate), there were 198 deaths from any cause and 41 from PC in the study period. Plasma 25(OH)D was not associated with all-cause or PC-specific mortality (p-values > 0·10). Plasma 1,25(OH)2D was inversely associated with all-cause mortality (HR for highest relative to lowest quartile = 0·45; 95% CI: 0·29-0·69), and PC-specific mortality (HR = 0·40; 95% CI: 0·14-1·19). These associations were apparent only in men with aggressive PC: all-cause mortality HR = 0·28 (95% CI·0·15-0·52; p-interaction = 0·07) and PC-specific mortality HR = 0·26 (95% CI: 0·07-1.00). Time spent outdoors was also associated with lower all-cause (HR for 4th relative to 1st exposure quartile = 0·42; 95% CI: 0·24-0·75) and PC-specific (HR = 0·48; 95% CI: 0·14-1·64) mortality, although the 95% CI for the latter was wide. The inverse association between post-treatment plasma 1,25(OH)2D levels and all-cause and PC-specific mortality in men with aggressive PC, suggest a possible beneficial effect of vitamin D supplementation in these men.

Objective Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. Methods Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. Results Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. Conclusions Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of ‘best buys’ for future decision-making in cervical cancer control.

Prostate cancer (PC) is the most common non-cutaneous cancer in men worldwide. The relationships between PC and possible risk factors for PC cases (n = 1,181) and male controls (n = 875) from the New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) were examined in this study. The associations between PC risk and paternal history of PC, body mass index (BMI), medical conditions, sexual behaviour, balding pattern and puberty, after adjusting for age, income, region of birth, place of residence, and PSA testing, were examined. Adjusted risk of PC was higher for men with a paternal history of PC (OR = 2.31; 95%CI: 1.70-3.14), personal history of prostatitis (OR = 2.30; 95%CI: 1.44-3.70), benign prostatic hyperplasia (OR = 2.29; 95%CI: 1.79-2.93), being overweight (vs. normal; OR = 1.24; 95%CI: 0.99-1.55) or obese (vs. normal; OR = 1.44; 95%CI: 1.09-1.89), having reported more than seven sexual partners in a lifetime (vs.

Background and aims: The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. Methods and results: 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women).Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. Conclusion: standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes

Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics. We also assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis, and they were inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features.

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

OBJECTIVE: To compare prostate cancer mortality for Aboriginal and non-Aboriginal men and to describe prostate cancer treatments received by Aboriginal men. PATIENTS AND METHODS: We analysed cancer registry records for all men diagnosed with prostate cancer in New South Wales (NSW) in 2001-2007 linked to hospital inpatient episodes and deaths. More detailed information on androgen-deprivation therapy and radiotherapy was obtained from medical records for 87 NSW Aboriginal men diagnosed in 2000-2011. The main outcomes were primary treatment for, and death from, prostate cancer. Analysis included Cox proportional hazards regression and logistic regression. RESULTS: There were 259 Aboriginal men among 35,214 prostate cancer cases diagnosed in 2001-2007. Age and spread of disease at diagnosis were similar for Aboriginal and non-Aboriginal men. Prostate cancer mortality 5 years after diagnosis was higher for Aboriginal men (17.5%, 95% confidence interval (CI) 12.4-23.3) than non-Aboriginal men (11.4%, 95% CI 11.0-11.8). Aboriginal men were 49% more likely to die from prostate cancer (hazard ratio 1.49, 95% CI 1.07-1.99) after adjusting for differences in demographic factors, stage at diagnosis, health access and comorbidities. Aboriginal men were less likely to have a prostatectomy for localised or regional cancer than non-Aboriginal men (adjusted odds ratio 0.60, 95% CI 0.40-0.91). Of 87 Aboriginal men with full staging and treatment information, 60% were diagnosed with localised disease. Of these, 38% had a prostatectomy (± radiotherapy), 29% had radiotherapy only and 33% had neither. CONCLUSION: More research is required to explain differences in treatment and mortality for Aboriginal men with prostate cancer compared with non-Aboriginal men. In the meantime, ongoing monitoring and efforts are needed to ensure Aboriginal men have equitable access to best care. This work was produced as part of the APOCC, which was funded by a National Health and MRC Health Services grant (Application Ref: 440202). Linkage of the ‘Patterns of Primary Treatment’ data set to the APDC was funded by a Cancer Institute NSW Epidemiology Linkage Grant (10/EPI/2-05).

Background: Organised cervical screening, introduced in 1991, appears to have reduced rates of cervical cancer incidence and mortality in women in Australia. This study aimed to assess whether cervical cancer rates in migrant women in the state of New South Wales (NSW) showed a similar pattern of change to that in Australian-born women after 1991. Methods: Data from the NSW Central Cancer Registry were obtained for females 15+ years diagnosed with invasive cervical cancer from 1973 to 2008 (N=11,485). We used joinpoint regression to assess annual percent changes (APC) in cervical cancer incidence and mortality before and after the introduction of organised cervical screening in 1991. Results: APC in incidence fell more rapidly after than before 1991 (p

BACKGROUND: Population-based patterns of care studies are important for monitoring cancer care but conducting them is expensive and resource-intensive. Linkage of routinely collected administrative health data may provide an efficient alternative. Our aim was to determine the accuracy of linked routinely collected administrative data for monitoring prostate cancer care in New South Wales (NSW), Australia. METHODS: The NSW Prostate Cancer Care and Outcomes Study (PCOS), a population-based survey of patterns of care for men aged less than 70 years diagnosed with prostate cancer in NSW, was linked to the NSW Cancer Registry, electronic hospital discharge records and Medicare and Pharmaceutical claims data from Medicare Australia. The main outcome measures were treatment with radical prostatectomy, any radiotherapy, external beam radiotherapy, brachytherapy or androgen deprivation therapy, and cancer staging. PCOS data were considered to represent the true treatment status. The sensitivity and specificity of the administrative data were estimated and relevant patient characteristics were compared using chi-squared tests. RESULTS: The validation data set comprised 1857 PCOS patients with treatment information linked to Cancer Registry records. Hospital and Medicare claims data combined described treatment more accurately than either one alone. The combined data accurately recorded radical prostatectomy (96% sensitivity) and brachytherapy (93% sensitivity), but not androgen deprivation therapy (76% sensitivity). External beam radiotherapy was rarely captured (5% sensitivity), but this was improved by including Medicare claims for radiation field setting or dosimetry (86% sensitivity). False positive rates were near 0%. Disease stage comparisons were limited by one-third of cases having unknown stage in the Cancer Registry. Administrative data recorded treatment more accurately for cases in urban areas. CONCLUSIONS: Cancer Registry and hospital inpatient data accurately captured radical prostatectomy and brachytherapy treatment, but not external beam radiotherapy or disease stage. Medicare claims data substantially improved the accuracy with which all major treatments were recorded. These administrative data combined are valid for population-based studies of some aspects of prostate cancer care

There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes. Copyright © 2010 UICC.

PURPOSE: To describe a methodology for surgical audit and feedback based on hospital-level indicators of the quality of colorectal cancer care. METHODS: Process and outcome indicators were identified from a population-based database (N = 3095 patients treated by 258 surgeons at 130 hospitals across New South Wales between February 1, 2000 and January 31, 2001). Hospitals were ranked on each indicator, with those in the lowest 20th percentile receiving a score of 0 and the remainder receiving a score of 1. Scores for individual indicators were then summed for each hospital and divided by the number of relevant indicators to provide an evidence-based score (EBS) and a clinical outcome score. RESULTS: Ten process and six clinical outcome indicators were identified. Hospital-level summary scores ranged from 0.14 to 1.0 for evidence-based processes and from 0.17 to 1.0 for clinical outcomes. Evidence-based score and clinical outcome score were independent (r = 0.12, P = 0.32). There was a small positive association between evidence-based score and caseload (r = 0.33, P = 0.005) but clinical outcome score and caseload were unrelated (r = 0.11, P = 0.36). CONCLUSIONS: Evidence-based score and clinical outcome score address different aspects of quality of care. The wide variability of hospitals' outcome scores and an association of evidence-based score and caseload indicate that simple scores may be useful in audit and feedback

Large-scale randomised controlled trials in Europe and the United States are informing evidence-based clinical advice

PURPOSE: It is important to meet the supportive care needs of cancer patients to ensure their satisfaction with their care. A population-wide sample of men younger than 70 years and newly diagnosed with prostate cancer was surveyed to determine their unmet needs in five domains and the factors predicting them. PATIENTS AND METHODS: Eligible men were younger than 70 years and residents in New South Wales, Australia, with newly diagnosed histopathologically confirmed prostate cancer. Sixty-seven percent of eligible men diagnosed between October 2000 and October 2001 participated. Demographic, treatment, and self-reported health data were collected. Information on cancer stage, grade, and prostate-specific antigen was obtained from medical records. Logistic regression analyses determined patient and treatment variables that predicted higher unmet needs. RESULTS: More than half (54%) of men with prostate cancer expressed some level of unmet psychological need, and 47% expressed unmet sexuality needs. Nearly one fourth expressed a moderate or high level of unmet need with respect to changes in sexuality. Sexuality needs were independently predicted by being younger, having had a secondary school education only, having had surgery, and being married, living as married, or divorced. Uncertainty about the future was also an important area of unmet need. CONCLUSION: Attention should be given to sexual and psychological needs in the early months after diagnosis or treatment of prostate cancer, particularly in younger men, those with less education, and those having surgery. Research into better ways of meeting these needs will enable us to meet them with as much rigor as we meet clinical treatment needs

We previously investigated the impact of health area of residence on colon and rectal cancer survival by estimating area-specific relative excess risk of death (RER), stratified by stage at diagnosis. The aims of this study were to quantify errors in colorectal cancer stage obtained from an Australian population-based cancer registry and assess the potential impact of errors in stage on these estimates. For a subset of cases, we compared the cancer registry stage with that from a survey of treating surgeons. We then randomly reallocated all cases to a simulated 'corrected' stage according to the estimated misclassification probabilities and repeated the analysis of area variation stratified by simulated stage 1,000 times. We found 70% agreement between the Registry and Survey stage. This reallocation of the Registry cases by stage resulted in substantial variation in area-specific RERs across the simulated samples. Area variation in survival for localized colon and localized rectal cancer, which were previously statistically significant when classified using Registry stage, appeared no longer to be so. Misclassification of cancer registry stage can have an important impact on estimates of spatial variation in stage-specific colon and rectal cancer survival. If population-based cancer registry data are to be effectively used in evaluating and improving cancer care, the quality of the stage data may need to be improved

Seasonal variation in cutaneous melanoma incidence with a summer peak is poorly understood. It has been hypothesized to be due to increased diagnosis in summer or a late-promoting effect of sun exposure. We analyzed the characteristics of incident cases of cutaneous melanoma and their outcome by season of diagnosis in the population of New South Wales, Australia. Cases of melanoma (25,845 cases; 10,869 females and 14,976 males) were registered by the New South Wales Central Cancer Registry in 1989 to 1998. There was significant seasonal variation in incidence (P < 0.0001, Nam test). The summer to winter ratio was greater for women, younger people, lesions on the limbs, and superficial spreading melanoma. Melanomas were thicker in winter than in summer (medians 0.75 and 0.70 mm, respectively; P < 0.0001, Kruskal-Wallis test). Cases were followed for a median of 63 months and 2,710 (10.5%) died from their melanoma. Fatality from melanoma was lower for melanomas diagnosed in summer than winter (relative fatality = 0.72; 95% confidence interval, 0.65-0.81); the 5-year survival rate was 92.1% for diagnosis in summer and 89.0% for diagnosis in winter. This result remained significant after adjustment for year of diagnosis, age, sex, Breslow thickness, anatomic location, and histologic type (relative fatality = 0.82; 95% confidence interval, 0.72-0.94). Seasonality in melanoma incidence is probably caused mainly by increased and earlier diagnosis in summer, although a late-stage promotional effect of sun exposure cannot be excluded completely. Earlier diagnosis may also reduce fatality when melanoma is diagnosed in summer. Independence of variation in fatality with season from seasonal variation in thickness, however, suggests that sun exposure around the time of diagnosis decreases fatality of melanoma

Survival from almost all cancers has improved during the last 30 years. There is debate over the reasons for the improvement. We examined trends in survival for 28 cancers from 1980 to 1996 in New South Wales (NSW), Australia, with adjustment for disease spread at diagnosis. NSW Central Cancer Registry data were used to estimate 5-year relative survival and relative excess risk of death for patients diagnosed in 1980-84, 1985-88, 1989-92 and 1993-96. Statistical significance of variation in excess deaths between periods of diagnosis was assessed using Poisson regression, with adjustment for age, sex, duration of follow-up, histology and spread of disease at diagnosis. There were statistically significant falls in excess deaths for 20 of the cancers with a 25% fall for all cancers combined. Cancers of the prostate, liver, thyroid, breast, gallbladder, body of uterus, rectum, cervix and ovary had falls of >30%. The falls varied by spread of disease; the largest being in localised and regionally spread tumours. Overall survival, when unadjusted for spread of cancer, generally fell in parallel with that in the specific categories of spread, which implies that stage migration did not contribute importantly to survival trends. While acknowledging the limitations of incomplete data on stage of cancer at diagnosis, we conclude that falls in excess deaths in NSW from 1980 to 1996 are unlikely, for many cancers, to be attributed to earlier diagnosis or stage migration; thus advances in cancer treatment have almost certainly contributed to them

Infections were examined as possible risk factors for non-Hodgkin lymphoma in a population-based case-control study in New South Wales and the Australian Capital Territory, Australia. Incident cases (n = 694) had no history of HIV infection or transplantation. Controls (n = 694) were randomly selected from electoral rolls and frequency matched to cases by age, sex, and area of residence. A postal questionnaire and telephone interview measured history of specific infections, occupational exposures, and behavioral and other risk factors for infection. Blood samples were tested for antibodies to human T-lymphotrophic virus type I and hepatitis C virus. Logistic regression models included the three matching variables and ethnicity. There was no association between risk of non-Hodgkin lymphoma and any of the variables analyzed, including sexually transmitted infections, sexual behavior, blood transfusions, influenza, acne, and either occupational or domestic exposure to zoonotic infections. Non-Hodgkin lymphoma risk was nonsignificantly elevated (odds ratio, 2.99; 95% confidence interval, 0.78-11.51) for those with a history of injecting drug use. Three cases and two controls (odds ratio, 1.32; 95% confidence interval, 0.22-7.98) tested positive to hepatitis C virus infection and none tested positive to human T-lymphotrophic virus type I/II infection. This study provides consistent evidence that sexually transmitted infections and zoonoses are not risk factors for non-Hodgkin lymphoma

In this study, we have investigated the impact of area of residence on survival from colon and rectal cancer. Relative survival and relative excess risk of death from cancer were calculated for each of 17 health areas in New South Wales, Australia. There were statistically significant differences in survival across areas for both cancers after adjusting for demographic factors. The variation remained for colon cancer but was reduced for rectal cancer after adjustment for spread of disease at diagnosis. This persistent variation in colon cancer survival suggests that variation in treatment contributes to it, and there is separate evidence for such variation. Of the 7186 patients whose deaths within five years were attributable to colorectal cancer, 784 could have had their survival increased to more than five years if the excess risk of death in all areas was reduced to the 20th centile of its distribution. Estimates such as this can assist in prioritizing improvements in cancer services

OBJECTIVE: Melanoma has been shown in numerous studies to be associated with sun exposure, and with host phenotypic factors of genetic origin. In this study we use information from a large series of incident cases of melanoma from an international population-based study to examine the patterns of incidence of melanoma in the first-degree relatives of these cases. METHODS: A total of 2508 incident cases of melanoma provided information on basic demographic data and pigmentary characteristics, in addition to detailed information on family history of melanoma. These data were used to examine the incidence rates ratios of melanoma in the relatives of cases in relation to population rates, and also with respect to phenotypic characteristics of the probands that have been shown to be associated with melanoma: mole counts, hair color, eye color, and skin sensitivity to the sun. RESULTS: The incidence rates reflect the underlying patterns of incidence in the source populations, with generally higher rates in the Australian sample, low rates in Italy, and intermediate rates in the USA and Canada. Also, rates are higher in men than in women, except at very young ages. Phenotypic characteristics of the probands were only weakly associated with the observed rates in the relatives although there is a strong inverse association with age at diagnosis. Cumulative risk of melanoma rises to 6.9% (6.1%) at age 80 in male (female) first-degree relatives of cases, and to 10.8% (9.5%) in relatives of cases diagnosed before age 50. CONCLUSIONS: Relatives of cases diagnosed with melanoma are at considerable lifetime risk of the disease, especially if the case is diagnosed at a young age

Routinely collected incidence data have often lacked specific identification of ocular melanoma in the past and with increasing diagnosis and management of this disease by noninvasive techniques may now underestimate the true incidence. We attempted to accurately measure the incidence of ocular melanoma in Australia from 1990 to 1998 using 2 population-based sources, cancer registries and ophthalmologists. We examined the distribution across the continent, by latitude and in subpopulations, and evaluated the extent of nonnotification to cancer registries. One-half (51%) of the incident cases from 1996 to 1998 were diagnosed clinically and had no tissue diagnosis. An estimated 20% of melanomas, mainly those lacking a tissue diagnosis, were not notified to Australian cancer registries, but only 1.3% were not notified by ophthalmologists. Expert reviewers agreed that a high proportion (95%) of clinically diagnosed lesions were probable or possible melanomas. Incidence was significantly higher in men than in women, especially at older ages, relatively uniform across the Australian states with only weak evidence of a latitude gradient, and higher in rural than in urban areas. The incidence of ocular melanoma in people born in Southern Europe was half and in those born in Asia only 20% of the rate in people born in Australia and New Zealand. We concluded that it was possible to identify a high proportion of cases by surveying relevant sources additional to cancer registries and to be reasonably confident of the accuracy of the clinical diagnoses. The higher incidence in older men, who probably have higher sun exposure, than in older women and in residents of rural areas, where outdoor work is more prevalent, than in urban areas; the low incidence in dark-eyed populations, who may have a lower sensitivity to or less transmission of solar radiation to the choroid; and the preferential location of ocular melanomas in ocular sites known to receive the highest exposure to solar radiation all support a role for solar radiation in the aetiology of ocular melanoma. The absence of a strong latitude gradient in incidence does not argue against such a role because exposure of the eye to solar UV is probably determined most by the horizon sky, where ambient solar UV is less affected by latitude