Genetics of melanoma predisposition

Hayward, Nicholas K.

doi:10.1038/sj.onc.1206445

Cited by 294 publications

(208 citation statements)

References 76 publications

(65 reference statements)

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“…Studies (GWAS) Melanoma sometimes develops within families (about 10 % of people with melanoma report a first-or second-degree relative with melanoma [99]), but this occurrence may be due to relatives sharing either genetic risk factors or environmental risk factors such as excessive sun exposure, or both. A population-based study of Australian twins estimated that 55 % of the variation in susceptibility to melanoma is due to genetic influences [215].…”

Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

“…The p14ARF protein induces cell cycle arrest or apoptosis via the p53 pathway. Mutations in the CDK4 gene are also associated with very high risk of melanoma, and the activities of CDK4 and p16 have similar downstream effects [99]. However, CDK4 mutations are very rare and only found in a handful of melanoma families worldwide [99].…”

Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

“…The melanocortin-1 receptor (MC1R) gene, which encodes the melanocytestimulating hormone receptor, was identified as the first low-to mediumpenetrance gene associated with melanoma risk [99,232]. It is one of the major genes that determine skin and hair colors, although there is evidence that it acts via pigmentary and non-pigmentary pathways to influence melanoma development [56, 120,201].…”

Section: Intermediate-risk Gene Variantsmentioning

confidence: 99%

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Melanoma Epidemiology and Prevention

Berwick

Buller

Cust

et al. 2015

Cancer Treatment and Research

122

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The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as

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Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

Section: Germline Genetic Factors and Genome-wide Associationmentioning

confidence: 99%

Section: Intermediate-risk Gene Variantsmentioning

confidence: 99%

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Melanoma Epidemiology and Prevention

Berwick

Buller

Cust

et al. 2015

Cancer Treatment and Research

122

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“…An established risk factor for CMM is a family history of the disease. Two high-penetrance susceptibility genes, CDKN2A (primarily the p16INK4A sequence) and CDK4, have been identified, but germ-line mutations in these genes account for merely one-third of highrisk families, implicating the existence of additional melanoma genes (Hayward, 2003).…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling of malignant melanoma using tiling-resolution arrayCGH

et al. 2007

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Malignant melanoma is an aggressive, heterogeneous disease where new biomarkers for diagnosis and clinical outcome are needed. We searched for chromosomal aberrations that characterize its pathogenesis using 47 different melanoma cell lines and tiling-resolution bacterial artificial chromosome-arrays for comparative genomic hybridization. Major melanoma genes, including BRAF, NRAS, CDKN2A, TP53, CTNNB1, CDK4 and PTEN, were examined for mutations. Distinct copy number alterations were detected, including loss or gain of whole chromosomes but also minute amplifications and homozygous deletions. Most common overlapping regions with losses were mapped to 9p24.3-q13, 10 and 11q14.1-qter, whereas copy number gains were most frequent on chromosomes 1q, 7, 17q and 20q. Amplifications were delineated to oncogenes such as MITF (3p14), CCND1 (11q13), MDM2 (12q15), CCNE1 (19q12) and NOTCH2 (1p12). Frequent findings of homozygous deletions on 9p21 and 10q23 confirmed the importance of CDKN2A and PTEN. Pair-wise comparisons revealed distinct sets of alterations, for example, mutually exclusive mutations in BRAF and NRAS, mutual mutations in BRAF and PTEN, concomitant chromosome 7 gain and 10 loss and concomitant chromosome 15q22.2-q26.3 gain and 20 gain. Moreover, alterations of the various melanoma genes were associated with distinct chromosomal imbalances suggestive of specific genomic programs in melanoma development.

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“…The additive versus multiplicative term refers to the mathematical effect of the relationship; additive modifiers are generally used to describe the effects of continuous variables, while multiplicative terms more often are used for stratified analyses [18]. Malignant melanoma is an example of a "requisite" gene-environment relationship: incidence is influenced by the degree of ultraviolet exposure in carriers of a mutation in a cell-cycle regulatory protein, CDKN2A [19]. Tobacco exposure and the risk of granulomatous lung diseases represent a susceptibility modifier.…”

Section: General Considerationsmentioning

confidence: 99%

Gene-environment interactions in sarcoidosis: challenge and opportunity

Culver¹,

Newman²,

Kavuru³

2007

Clinics in Dermatology

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Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of geneenvironment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes.

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Genetics of melanoma predisposition

Cited by 294 publications

References 76 publications

Melanoma Epidemiology and Prevention

Melanoma Epidemiology and Prevention

Genomic profiling of malignant melanoma using tiling-resolution arrayCGH

Gene-environment interactions in sarcoidosis: challenge and opportunity

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