Search for genetic variants associated with cutaneous malignant melanoma in the Ashkenazi Jewish population

Loo, Joanne C. Y.; Paterson, Andrew D.; Hao, Ai Hua; Shennan, Michael; Peretz, Hava; Sidi, Yael; Hogg, David; Yakobson, Emanuel

doi:10.1136/jmg.2004.027300

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…Lack of germline mutations in the CDKN2A/ARF and CDK4 loci has been recently reported by Loo et al (2005) among 22 Ashkenazi Jewish families with an apparent inherited predisposition to melanoma. Taken together with the data reported herein, it appears that in over 60 Ashkenazi Jewish melanoma families, no germline alteration in CDKN2A/ARF and CDK4 loci underlie the apparent predisposition.…”

Section: Discussionmentioning

confidence: 94%

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours

et al. 2005

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To gain insight into the molecular mechanisms involved in the inherited predisposition to melanoma and associated neural system tumours, 42 Jewish, mainly Ashkenazi, melanoma families with or without neural system tumours were genotyped for germline point mutations and genomic deletions at the CDKN2A/ARF and CDK4 loci. CDKN2A/ARF deletion detection was performed using D9S1748, an intragenic microsatellite marker. Allele dosage at the p14 ARF locus was analysed by quantitative real-time PCR employing a TaqMan probe that anneals specifically to exon 1b of the p14 ARF gene. For detecting point mutations, dHPLC and direct sequencing of the coding sequences of CDKN2A/ARF and CDK4 was used. No germline alterations in any of the tested genes were detected among the families under study. We conclude that in the majority of Ashkenazi Jewish families, the genes tested are unlikely to be implicated in the predisposition to melanoma and associated neural system tumours.

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Section: Discussionmentioning

confidence: 94%

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours

et al. 2005

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“…Inherited predisposition to cancer is a well-known contributor to the cancer burden in Caucasians of Ashkenazi Jewish (AJ) descent, specifically in breast and ovarian cancers [14,15,16]. Recent epidemiologic data also suggest that the incidence of melanoma in Ashkenazi Jews is relatively high [17,18]. Although breast and ovarian cancers have been extensively studied in people of AJ ancestry, there has been no report to date that focuses on the primary tumor characteristics and prognosis of AJ patients with melanoma [19].…”

Section: Introductionmentioning

confidence: 99%

Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients

et al. 2016

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Objectives: The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. Methods: We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the χ² test and multivariate logistic regression. We compared survival distributions using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard ratios. Results: Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. Conclusion: Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background.

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“…African-Americans, in whom the G allele is extremely rare, have a markedly low incidence of MM [9][10][11]; the Japanese population, in whom there is a high prevalence of this allele, generally has a very low incidence of MM but a high incidence of skin cancer in those regions of the world where there is increased exposure to sunlight [12,13]. Ashkenazi Jews, who have a high incidence of MM [14], also harbor a high rate of G309 polymorphism [8].…”

Section: Discussionmentioning

confidence: 96%

“…Last bar represents the G309 prevalence in our cohort of 28 MM patients. (b) Average MM annual age-adjusted incidence, averaged from several references: Caucasians, Japanese [12,19], American-Africans [10,11], Ashkenazi Jews [14]. Caucasians from North America and Western Europe were regarded as one group, as the differences among the various subgroups in this population in terms of MM incidence are minor compared with the differences among the ethnic groups outlined in this figure.…”

Section: (B)mentioning

confidence: 99%

Germline analysis of thymidine/guanidine polymorphism at position 309 of the Mdm2 promoter in malignant melanoma patients

Gluck¹,

Simon

Catane³

et al. 2009

Melanoma Research

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p53 is a major tumor suppressor gene, frequently mutated in human cancer, but rarely mutated in malignant melanoma (MM). Mdm2, the major negative regulator of p53, is overexpressed in 50-60% of MM patients, by an unknown mechanism. Single nucleotide polymorphism at position 309 of the Mdm2 promoter correlates with increased Mdm2 levels and reduced p53 activation. We speculated that guanine at position 309 (G309) of the Mdm2 promoter might be a cause of Mdm2 overexpression in MM patients, and associated with increased risk of MM. We aimed to estimate the prevalence of G309 in MM patients. Genomic DNA was collected from a cohort of 28 MM patients of various clinical stages. The relevant DNA stretch was sequenced and thymidine/guanidine polymorphism at position 309 of Mdm2 promoter was examined. We compared the resultant frequencies with the frequencies reported in the literature for the general population. The G allele frequency in the cohort of MM patients was 0.518. This frequency is high compared with the reported frequency of 0.351 in Caucasian healthy populations (odds ratio=1.98, P=0.014). It is also higher than a G allele frequency of 0.464 reported for Ashkenazi Jewish women, although this comparison was not statistically significant (odds ratio=1.14, P=0.76). These results suggest that the single nucleotide polymorphism G309 in the Mdm2 promoter might be an important genetic predisposing factor, and possibly indicate a molecular mechanism of disease regarding MM. These results must be confirmed in a larger cohort of MM patients and controls.

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Search for genetic variants associated with cutaneous malignant melanoma in the Ashkenazi Jewish population

Cited by 4 publications

References 11 publications

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours

Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients

Germline analysis of thymidine/guanidine polymorphism at position 309 of the Mdm2 promoter in malignant melanoma patients

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