Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

BACKGROUND: Melanoma 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. OBJECTIVES: We 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. METHODS: We 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. RESULTS: When 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 < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

High variability in anatomic patterns of cutaneous photodamage: a population-based study.

BACKGROUND: Skin cancer is strongly associated with photodamaged skin, but body sites are often referred to as 'exposed' or 'unexposed' to sun without recognizing extent of site-specific variation. OBJECTIVES: To assess whole-body patterns of photodamage in an Australian population. METHODS: A random sample of adult residents of Queensland underwent imaging across 10 body sites. Photodamage was graded from images using an ordinal photonumeric scale. We used cluster analysis to identify whole-body photodamage patterns and prevalence proportion ratios (PPRs) to assess associated factors. RESULTS: Of 190 adults (median age 52; 58% males), 58% showed severe or moderate-to-severe photodamage on most body sites. A higher proportion of woman had severe photodamage on the arms (upper: P = 0.002, lower: P = 0.034). A higher proportion of men had moderate or severe photodamage on the lower back (P = 0.004). We identified four photodamage patterns: 'severe general' (n = 24, 13%), 'moderate-severe general' (n = 86, 45%), 'moderate-severe v-neck' (n = 40, 21%) and 'mild-moderate upper body' (n = 12, 6%). All participants with 'severe-general' photodamage were >50 years and more likely to have past skin cancer (PPR: 2.54, 95% CI: 1.44-4.49) than those with 'moderate-severe v-neck' photodamage. Those with 'moderate-severe general' photodamage showed similar associations and were more likely female (PPR: 1.33, 95% CI: 1.04-1.69). Past or current smoking was associated with having higher levels of photodamage, with no smokers in those with 'mild-moderate upper body' photodamage. CONCLUSIONS: Moderate-to-severe photodamage across much of the body is common in Queensland adults and associated with age, sex, past skin cancer and smoking. Assuming a universal pattern of site-specific sun exposure could lead to spurious correlations, while accurate and objective assessment of site-specific photodamage can add to understanding of the development of sun-associated skin cancers, in particular site-specific skin carcinogenesis. Additionally, degree of site-specific photodamage has the potential to assist skin cancer screening.

Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

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.

Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure.

BACKGROUND: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. OBJECTIVE: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. METHODS: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. RESULTS: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. CONCLUSIONS: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Variations in outcomes for Indigenous women with breast cancer in Australia: A systematic review.

This systematic review examines variations in outcomes along the breast cancer continuum for Australian women by Indigenous status. Multiple databases were systematically searched for peer-reviewed articles published from 1 January 1990 to 1 March 2015 focussing on adult female breast cancer patients in Australia and assessing survival, patient and tumour characteristics, diagnosis and treatment by Indigenous status. Sixteen quantitative studies were included with 12 rated high, 3 moderate and 1 as low quality. No eligible studies on referral, treatment choices, completion or follow-up were retrieved. Indigenous women had poorer survival most likely reflecting geographical isolation, advanced disease, patterns of care, comorbidities and disadvantage. They were also more likely to be diagnosed when younger, have advanced disease or comorbidities, reside in disadvantaged or remote areas, and less likely to undergo mammographic screening or surgery. Despite wide heterogeneity across studies, an overall pattern of poorer survival for Indigenous women and variations along the breast cancer continuum of care was evident. The predominance of state-specific studies and small numbers of included Indigenous women made forming a national perspective difficult. The review highlighted the need to improve Indigenous identification in cancer registries and administrative databases and identified key gaps notably the lack of qualitative studies in current literature.

A systematic review of inequalities in psychosocial outcomes for women with breast cancer according to residential location and Indigenous status in Australia.

BACKGROUND: The aim of this systematic review was to examine variations in psychosocial outcomes by residential location and Indigenous status in women diagnosed with breast cancer (BC) in Australia. METHODS: Systematic searches were undertaken using multiple databases covering articles between 1 January 1990 and 1 March 2015 focusing on adult women with BC in an Australian setting and measuring quality of life (QOL), psychological distress or psychosocial support. RESULTS: Thirteen quantitative and three qualitative articles were included. Two quantitative and one qualitative article were rated high quality, seven moderate and the remaining were low quality. No studies examining inequalities by Indigenous status were identified. Non-metropolitan women were more likely to record lower QOL relating to breast cancer-specific concerns and reported a lack of information and resources specific to their needs. Continuity of support, ongoing care and access to specialist and allied health professionals were major concerns for non-metropolitan women. Non-metropolitan women identified unmet needs in relation to travel, fear of cancer recurrence and lack of psychosocial support. CONCLUSIONS: Overall, there was a lack of evidence relating to variations in psychosocial outcomes for women with BC according to residential status or Indigenous status. While the review identified some specific concerns for non-metropolitan women with BC, it was limited by the lack of good quality studies using standardised measures. Copyright © 2016 John Wiley & Sons, Ltd.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice.

BACKGROUND: Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. OBJECTIVES: To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. METHODS: This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. RESULTS: Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. CONCLUSIONS: More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

Population-based survival estimates for childhood cancer in Australia during the period 1997-2006.

BACKGROUND: This study provides the latest available relative survival data for Australian childhood cancer patients. METHODS: Data from the population-based Australian Paediatric Cancer Registry were used to describe relative survival outcomes using the period method for 11,903 children diagnosed with cancer between 1983 and 2006 and prevalent at any time between 1997 and 2006. RESULTS: The overall relative survival was 90.4% after 1 year, 79.5% after 5 years and 74.7% after 20 years. Where information onstage at diagnosis was available (lymphomas, neuroblastoma, renal tumours and rhabdomyosarcomas), survival was significantly poorer for more-advanced stage. Survival was lower among infants compared with other children for those diagnosed with leukaemia, tumours of the central nervous system and renal tumours but higher for neuroblastoma. Recent improvements in overall childhood cancer survival over time are mainly because of improvements among leukaemia patients. CONCLUSION: The high and improving survival prognosis for children diagnosed with cancer in Australia is consistent with various international estimates. However, a 5-year survival estimate of 79% still means that many children who are diagnosed with cancer will die within 5 years, whereas others have long-term health morbidities and complications associated with their treatments. It is hoped that continued developments in treatment protocols will result in further improvements in survival.

Trends in incidence of childhood cancer in Australia, 1983-2006.

BACKGROUND: There are few population-based childhood cancer registries in the world containing stage and treatment data. METHODS: Data from the population-based Australian Paediatric Cancer Registry were used to calculate incidence rates during the most recent 10-year period (1997-2006) and trends in incidence between 1983 and 2006 for the 12 major diagnostic groups of the International Classification of Childhood Cancer. RESULTS: In the period 1997-2006, there were 6184 childhood cancer (at 0-14 years) cases in Australia (157 cases per million children). The commonest cancers were leukaemia (34%), that of the central nervous system (23%) and lymphomas (10%), with incidence the highest at 0-4 years (223 cases per million). Trend analyses showed that incidence among boys for all cancers combined increased by 1.6% per year from 1983 to 1994 but have remained stable since. Incidence rates for girls consistently increased by 0.9% per year. Since 1983, there have been significant increases among boys and girls for leukaemia, and hepatic and germ-cell tumours, whereas for boys, incidence of neuroblastomas and malignant epithelial tumours has recently decreased. For all cancers and for both sexes combined, there was a consistent increase (+0.7% per year, 1983-2006) at age 0-4 years, a slight non-significant increase at 5-9 years, and at 10-14 years, an initial increase (2.7% per year, 1983-1996) followed by a slight non-significant decrease. CONCLUSION: Although there is some evidence of a recent plateau in cancer incidence rates in Australia for boys and older children, interpretation is difficult without a better understanding of what underlies the changes reported.

Completeness of histopathology reporting of melanoma in a high-incidence geographical region.

BACKGROUND: Appropriate histopathology reporting helps to ensure effective therapy and prognosis. OBJECTIVE: To examine compliance with clinical practice guidelines for histopathology reports of melanomas. METHODS: A sample of melanoma histopathology reports in Queensland was audited for inclusion of recommended information. The quality of documentation was constructed and multivariate analysis used to determine factors affecting the quality of reporting practices. RESULTS: Documentation of the most important features of melanoma was high: clear diagnosis (99.8%; 95% CI 98.6-100), thickness (99.8%; 95% CI 98.6-100), comment on adequacy of excision (87.9%; 95% CI 84.9-91.0) and measurement of margins (91.9%; 95% CI 88.8-91.4). Overall reporting of ulceration and regression was of lesser completeness (83.0 and 77.8%, respectively) and these features were more likely to be reported by high-volume laboratories (p < 0.001 and p = 0.037, respectively). This trend was not apparent for other features. Fewer than 50% of reports documented mitotic rate per square millimetre, predominant cell type, microsatellites, growth phase and desmoplasia. CONCLUSION: Awareness of current reporting practices and identification of areas in which insufficiencies exist enable the revision of systems and potential improvements to the transfer of information to treating clinicians.

Accuracy of case-reported family history of melanoma in Queensland, Australia.

A positive family history is used in clinical practice as an indication of increased melanoma risk, yet there are no data on the accuracy of reported family histories of melanoma. The validity of case-reported family history of melanoma was assessed in the course of a family and twin study of melanoma in Queensland, Australia, conducted among the families of 2,118 melanoma cases diagnosed in Queensland between 1982 and 1990. A total of 913 melanoma cases made 1,267 reports of melanoma among their first-degree relatives. A total of 1,040 of these reports were checked, first through relatives themselves and then, if the relative also said they had had melanoma, through the relative's medical records. Medical confirmation of melanoma as the diagnosis was obtained for 623 reports (59.9%; 95% confidence interval 56.9-62.9): a false-positive reporting rate by cases of 40.1%. The level of false-positive reporting was lower for cases under 70 years of age, for women, for cases whose own diagnosis of melanoma was more than 5 years earlier, and for cases with three or more relatives with melanoma. Media campaigns in Queensland aimed at increasing skin cancer awareness, and confusion between melanoma and other more common actinic neoplasma (basal and squamous cell carcinomas), may partly explain the high false-positive reporting rate observed here. For this reason, It is difficult to generalize these findings to northern hemisphere populations where skin cancer is not such an important public health issue.

The Queensland Familial Melanoma Project: study design and characteristics of participants.

Family history of melanoma is associated with an increased risk for the disease. Neither the relative contributions of genetic and shared environmental factors to familial risk nor how genetic susceptibility is mediated are known. The Queensland Familial Melanoma Project was undertaken to investigate (a) the role of genetic susceptibility as indicated by skin type, pigmentation and the prevalence of naevi and (b) exposure to solar ultraviolet radiation, and their interaction in the aetiology of familial melanoma. After obtaining doctor's consent, a brief family history questionnaire was mailed to all Queensland residents with a first primary cutaneous melanoma diagnosed between 1982 and 1990. Detailed information on melanoma history and standard melanoma risk factors was sought from all responding twins and familial cases, from a sample of non-familial cases and from cases' relatives. Medical confirmation was sought for all relatives reported to have had melanoma. The final sample comprises 15,907 persons in the 1,912 families of 2,118 melanoma cases, including 509 families in which there are two or more individuals with confirmed melanoma. Melanoma history and risk factors were obtained for 9,746 relatives, including 94 twins of cases. This is the largest family and twin study of cutaneous melanoma yet conducted in an unselected, geographically-defined population. We describe the design of the study and the characteristics of the total study population.

Ocular melanoma is not associated with CDKN2A or MC1R variants--a population-based study.

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and there were no significant differences in the frequency of any of the five most common variants of MC1R. We also found no significant differences between cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. Our findings argue against an important predisposing effect of the MC1R and CDKN2A genes for ocular melanoma.

A randomised trial of population screening for melanoma.

OBJECTIVES: Melanoma is a significant cause of morbidity and mortality worldwide and incidence is increasing. Survival after treatment is inversely related to the thickness of the tumour at diagnosis. Population screening has the potential to reduce mortality but there is no conclusive evidence of benefit. Such evidence can come best from a randomised trial. Here we describe the design of a community based randomised trial of a population screening programme for melanoma in Queensland, Australia and early results of the first phase of the trial. METHODS: A total of 44 communities (aggregate population 560 000 adults aged 30 years or more) will be randomised to receive either a community based screening programme for 3 years or normal practice. The screening programme promotes thorough skin self examination and whole body skin examination by a doctor and provides open access skin cancer screening clinics. In its first phase, the trial is underway in nine intervention and nine control communities. The primary outcome measure is mortality from melanoma during 15 years of follow up. RESULTS: The first phase of the trial has shown the feasibility of implementing a population skin screening programme including regular skin cancer screening clinics, and has shown the strong support of communities and doctors for the programme. There has been a significant 2.5-fold increase in participation in screening in the intervention communities in this first phase after the first 12 months of the trial and no significant increase in participation in screening in control communities during this period. CONCLUSIONS: The design of a community based randomised trial of screening for melanoma has been successfully peer reviewed and the intervention has been shown to be feasible in practice. This randomised trial may be one of the last opportunities to develop the evidence required for public health recommendations for population screening for melanoma.