Melbourne School of Population and Global Health - Research Publications

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    The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival.
    Orlow, I ; Shi, Y ; Kanetsky, PA ; Thomas, NE ; Luo, L ; Corrales-Guerrero, S ; Cust, AE ; Sacchetto, L ; Zanetti, R ; Rosso, S ; Armstrong, BK ; Dwyer, T ; Venn, A ; Gallagher, RP ; Gruber, SB ; Marrett, LD ; Anton-Culver, H ; Busam, K ; Begg, CB ; Berwick, M ; GEM Study Group, (Wiley, 2018-03)
    Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p < .05). These SNPs, and a haplotype, had a statistically significant association with survival among subjects exposed to high UVB in multivariable regression models and exerted their effect in the opposite direction among those with low UVB. SNPs rs1544410/BsmI and rs731236/TaqI remained significant after adjustment for multiple testing. These results suggest that the association between VDR and melanoma-specific survival is modified by sun exposure around diagnosis, and require validation in an independent study. Whether the observed effects are dependent or independent of vitamin D activation remains to be determined.
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    Does personalized melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?
    Smit, AK ; Keogh, LA ; Newson, AJ ; Butow, PN ; Dunlop, K ; Morton, RL ; Kirk, J ; Espinoza, D ; Cust, AE (OXFORD UNIV PRESS, 2017-09)
    BACKGROUND: Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. OBJECTIVES: To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. METHODS: We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n = 103, aged 21-69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. RESULTS: From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. CONCLUSIONS: Personalized melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.
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    Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.
    Watts, CG ; Madronio, CM ; Morton, RL ; Goumas, C ; Armstrong, BK ; Curtin, A ; Menzies, SW ; Mann, GJ ; Thompson, JF ; Cust, AE (Wiley, 2017-11)
    BACKGROUND/OBJECTIVES: To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. METHODS: The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). RESULTS: Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. CONCLUSIONS: Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk.
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    Nevus count associations with pigmentary phenotype, histopathological melanoma characteristics and survival from melanoma.
    Taylor, NJ ; Thomas, NE ; Anton-Culver, H ; Armstrong, BK ; Begg, CB ; Busam, KJ ; Cust, AE ; Dwyer, T ; From, L ; Gallagher, RP ; Gruber, SB ; Nishri, DE ; Orlow, I ; Rosso, S ; Venn, AJ ; Zanetti, R ; Berwick, M ; Kanetsky, PA ; GEM Study Group, (Wiley, 2016-09-15)
    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.
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    Economic evaluations of psychosocial interventions in cancer: a systematic review.
    Dieng, M ; Cust, AE ; Kasparian, NA ; Mann, GJ ; Morton, RL (Wiley, 2016-12)
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    Beyond country-specific incidence and mortality: the global burden of melanoma.
    Bell, KJL ; Cust, AE (Oxford University Press (OUP), 2018-02)
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    Prognostic features for acral lentiginous melanoma.
    Cust, AE (Oxford University Press (OUP), 2018-02)
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    Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis.
    Liyanage, UE ; Law, MH ; Ong, JS ; Cust, AE ; Mann, GJ ; Ward, SV ; Melanoma Meta-Analysis Consortium, ; Gharahkhani, P ; Iles, MM ; MacGregor, S (Wiley, 2018-08-01)
    Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk, putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomized controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma. To perform MR, we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17th percentile to the median. Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk: odds ratio [OR] = 1.03 (95% confidence interval [CI] = 0.96-1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small.
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    Validation of Questionnaire and Diary Measures of Time Outdoors Against an Objective Measure of Personal Ultraviolet Radiation Exposure.
    Cust, AE ; Fenton, GL ; Smit, AK ; Espinoza, D ; Dobbinson, S ; Brodie, A ; Dang, HTC ; Kimlin, MG (Wiley, 2018-07)
    Self-reported sun exposure is commonly measured using questionnaires or diaries, but there are limited data on their validity, particularly for population subgroups. This research aimed to compare self-reported sun exposure, measured as (1) habitual time outdoors over the past month on weekends and weekdays and (2) a 4-day diary measure, against objective measurement of personal ultraviolet radiation using polysulfone film dosimeters. From November 2015 to January 2016, 94 people (22-69 years and living in New South Wales, Australia) completed a questionnaire, 4-day diary and 4-day dosimeter measures of overall, weekday and weekend sun exposure. Spearman correlations and Bland-Altman plots were used to measure agreement. The overall weekly correlation was 0.57 (95% confidence interval [CI] 0.44, 0.68) between standard erythemal doses (SEDs) measured by dosimeter and time spent outdoors measured by questionnaire, 0.74 (95% CI 0.66-0.81) between dosimeter and diary, and 0.59 (95% CI 0.48-0.68) between questionnaire and diary measures. Validity was lower for younger people and weekend sun exposure. There was strong correlation between dosimeter and sun diary measures and moderate correlation between dosimeter and questionnaire measures. Daily measurement over a longer period may be required to accurately capture weeklong sun exposure in all population subgroups.