Background Melanocortin-1 receptor (MC1R) gene variants are very common and are associated with melanoma risk, but their contribution to melanoma risk prediction compared with traditional risk ...factors is unknown. We aimed to 1) evaluate the separate and incremental contribution of MC1R genotype to prediction of early-onset melanoma, and compare this with the contributions of physician-measured and self-reported traditional risk factors, and 2) develop risk prediction models that include MC1R, and externally validate these models using an independent dataset from a genetically similar melanoma population. Methods Using data from an Australian population-based, case-control-family study, we included 413 case and 263 control participants with sequenced MC1R genotype, clinical skin examination and detailed questionnaire. We used unconditional logistic regression to estimate predicted probabilities of melanoma. Results were externally validated using data from a similar study in England. Results When added to a base multivariate model containing only demographic factors, MC1R genotype improved the area under the receiver operating characteristic curve (AUC) by 6% (from 0.67 to 0.73; P 0.001) and improved the quartile classification by a net 26% of participants. In a more extensive multivariate model, the factors that contributed significantly to the AUC were MC1R genotype, number of nevi and previous non-melanoma skin cancer; the AUC was 0.78 (95% CI 0.75-0.82) for the model with self-reported nevi and 0.83 (95% CI 0.80-0.86) for the model with physician-counted nevi. Factors that did not further contribute were sun and sunbed exposure and pigmentation characteristics. Adding MC1R to a model containing pigmentation characteristics and other self-reported risk factors increased the AUC by 2.1% (P = 0.01) and improved the quartile classification by a net 10% (95% CI 1-18%, P = 0.03). Conclusions Although MC1R genotype is strongly associated with skin and hair phenotype, it was a better predictor of early-onset melanoma than was pigmentation characteristics. Physician-measured nevi and previous non-melanoma skin cancer were also strong predictors. There might be modest benefit to measuring MC1R genotype for risk prediction even if information about traditional self-reported or clinically measured pigmentation characteristics and nevi is already available. Keywords: MC1R, Risk prediction, Accuracy, Melanoma, Sun exposure, Early-onset, Pigmentation, Nevi
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Issue addressed: Australia records the highest incidence of skin cancer in the world. In response to this, public education campaigns have incorporated messages about reducing sun exposure and ...avoiding sunburn. This study sought to describe the prevalence of and factors associated with sunburn in Queensland residents.Methods: The Queensland Cancer Risk Study was a population-based, cross-sectional survey of 9,298 respondents conducted via computer-assisted telephone interview during 2004. Sunburn prevalence and its association with socio-demographics and skin cancer risk variables were examined.Results: More than two-thirds (70.4%) of respondents reported at least one episode of sunburn in the past 12 months, and one in 10 respondents reported at least one episode of severe sunburn in the past 12 months. Experiences of sunburn on two or more occasions were reported more frequently by males than females (57.6% versus 46.5%, p<0.001), and by nearly two-thirds (65.8%) of those aged 20-39 years compared to 48.0% of 40-59 year olds, and 26.7% of 60-75 year olds (p< 0.001) Episodes of sunburn were strongly associated with being male (OR=2.20 95%CI 1.84-2.63) and being aged 20 to 39 years compared to 60 to 75 years (OR=9.79, 95%CI=7.66-12.50).Conclusions: Sunburn remains highly prevalent among Queensland residents particularly among men and in the younger age groups.
We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control ...individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10−5 and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10−3: an SNP in ATM (rs1801516, overall P = 3.4 × 10−9), an SNP in MX2 (rs45430, P = 2.9 × 10−9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10−10). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10−7 under a fixed-effects model and P = 1.2 × 10−3 under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
Herein is described a general sampling protocol that includes culture, differentiation and fixing of cells in their preferred morphology on the one sample substrate (Si
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) to enable subsequent ...diverse modern microspectroscopic analyses. The protocol enables unprecedented correlated and complementary information on the intracellular biochemistry of metabolic processes, diseases and their treatment, which offers the opportunity to revolutionize our understanding of cell and tissue biology at a molecular level. The culture of adherent cells onto inexpensive Si
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membranes allows microspectroscopic analyses across the electromagnetic spectrum, from hard X-ray fluorescence (both XRF and XANES), through to visible and fluorescence light microscopies, and infrared microspectroscopy without substrate interference. Adherent mammalian cell lines (3T3-L1 adipocytes and H9c2 cardiac myocytes) illustrate the
in vitro
application of these protocols. The cells adhered strongly to Si
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membranes and visually displayed normal proliferative and phenotypic growth; more importantly, rapid alcohol fixation of cells did not affect their structural integrity for subsequent analyses.
A versatile sampling protocol is presented for diverse microspectroscopic studies of cells, such as adipocytes, in their preferred morphologies on silicon nitride windows.
Issue addressed: Australia records the highest incidence of skin cancer in the world. In response to this, public education campaigns have incorporated messages about reducing sun exposure and ...avoiding sunburn. This study sought to describe the prevalence of and factors associated with sunburn in Queensland residents.Methods: The Queensland Cancer Risk Study was a population-based, cross-sectional survey of 9,298 respondents conducted via computer-assisted telephone interview during 2004. Sunburn prevalence and its association with socio-demographics and skin cancer risk variables were examined.Results: More than two-thirds (70.4%) of respondents reported at least one episode of sunburn in the past 12 months, and one in 10 respondents reported at least one episode of severe sunburn in the past 12 months. Experiences of sunburn on two or more occasions were reported more frequently by males than females (57.6% versus 46.5%, p<0.001), and by nearly two-thirds (65.8%) of those aged 20-39 years compared to 48.0% of 40-59 year olds, and 26.7% of 60-75 year olds (p< 0.001) Episodes of sunburn were strongly associated with being male (OR=2.20 95%CI 1.84-2.63) and being aged 20 to 39 years compared to 60 to 75 years (OR=9.79, 95%CI=7.66-12.50).Conclusions: Sunburn remains highly prevalent among Queensland residents particularly among men and in the younger age groups.
Issue addressed: Australia records the highest incidence of skin cancer in the world. In response to this, public education campaigns have incorporated messages about reducing sun exposure and ...avoiding sunburn. This study sought to describe the prevalence of and factors associated with sunburn in Queensland residents.Methods: The Queensland Cancer Risk Study was a population-based, cross-sectional survey of 9,298 respondents conducted via computer-assisted telephone interview during 2004. Sunburn prevalence and its association with socio-demographics and skin cancer risk variables were examined.Results: More than two-thirds (70.4%) of respondents reported at least one episode of sunburn in the past 12 months, and one in 10 respondents reported at least one episode of severe sunburn in the past 12 months. Experiences of sunburn on two or more occasions were reported more frequently by males than females (57.6% versus 46.5%, p<0.001), and by nearly two-thirds (65.8%) of those aged 20-39 years compared to 48.0% of 40-59 year olds, and 26.7% of 60-75 year olds (p< 0.001) Episodes of sunburn were strongly associated with being male (OR=2.20 95%CI 1.84-2.63) and being aged 20 to 39 years compared to 60 to 75 years (OR=9.79, 95%CI=7.66-12.50).Conclusions: Sunburn remains highly prevalent among Queensland residents particularly among men and in the younger age groups.
Issue addressed: Australia records the highest incidence of skin cancer in the world. In response to this, public education campaigns have incorporated messages about reducing sun exposure and ...avoiding sunburn. This study sought to describe the prevalence of and factors associated with sunburn in Queensland residents.Methods: The Queensland Cancer Risk Study was a population-based, cross-sectional survey of 9,298 respondents conducted via computer-assisted telephone interview during 2004. Sunburn prevalence and its association with socio-demographics and skin cancer risk variables were examined.Results: More than two-thirds (70.4%) of respondents reported at least one episode of sunburn in the past 12 months, and one in 10 respondents reported at least one episode of severe sunburn in the past 12 months. Experiences of sunburn on two or more occasions were reported more frequently by males than females (57.6% versus 46.5%, p<0.001), and by nearly two-thirds (65.8%) of those aged 20-39 years compared to 48.0% of 40-59 year olds, and 26.7% of 60-75 year olds (p< 0.001) Episodes of sunburn were strongly associated with being male (OR=2.20 95%CI 1.84-2.63) and being aged 20 to 39 years compared to 60 to 75 years (OR=9.79, 95%CI=7.66-12.50).Conclusions: Sunburn remains highly prevalent among Queensland residents particularly among men and in the younger age groups.
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