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

Vajdic, Claire M.; Kricker, Anne; Duffy, David L.; Aitken, Joanne F.; Stark, Mitchell; Huurne, Jac ter; Martin, Nicholas G.; Armstrong, Ben; Hayward, N. K.

doi:10.1097/00008390-200308000-00011

Cited by 13 publications

(7 citation statements)

References 24 publications

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“…This suggests that certain MC1R variants can exert an effect on melanoma tumorigenesis in a dual manner, both as a determinant of fair skin and as a component in an independent additional pathway (Palmer et al, 2000;Van der Velden et al, 2001). Our data support the findings of Metzelaar-Blok et al (2001) and the recent study reported by Vajdic et al (2003), who found no relationship between variation in MC1R and risk of uveal melanoma. Moreover, pooling data from all three studies provide no evidence that variants confer an increased risk of uveal melanoma.…”

Section: Discussionsupporting

confidence: 93%

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Role of MC1R variants in uveal melanoma

et al. 2003

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Variants of the melanocortin-1 receptor (MC1R) gene have been linked to sun-sensitive skin types and hair colour, and may independently play a role in susceptibility to cutaneous melanoma. To assess the role of MC1R variants in uveal melanoma, we have analysed a cohort of 350 patients for the changes within the major region of the gene displaying sequence variation. Eight variants were detected -V60L, D84E, V92M, R151C, I155T, R160W, R163Q and D294H -63% of these patients being hetero-or homozygous for at least one variant. Standard melanoma risk factor data were available on 119 of the patients. MC1R variants were significantly associated with hair colour (P ¼ 0.03) but not skin or eye colour. The frequency of the variants detected in the 350 patients was comparable with those in the general population, and comparison of the cumulative tumour distribution by age at diagnosis in carriers and noncarriers provided no evidence that MC1R variants confer an increased risk of uveal melanoma. We interpret the data as indicating that MC1R variants do not appear to be major determinants of susceptibility to uveal melanoma.

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Section: Discussionsupporting

confidence: 93%

“…Two research groups have previously reported on the relationship between MC1R variants and risk of uveal melanomaMetzelaar-Blok et al (2001) based on analysis of 162 patients and Vajdic et al (2003) based on analysis of 62 patients. In both studies, there was no difference in the frequency of variants in cases compared to controls.…”

Section: Resultsmentioning

confidence: 99%

Role of MC1R variants in uveal melanoma

et al. 2003

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“…There is no statistically significant association of the MC1R variants with ocular melanoma in both studies. 41,42 This could be the consequence of strata with small numbers of cases and controls with the respective genotypes in both analyses, and it does not necessarily rule out a possible association between MC1R variants and uveal melanoma risk.…”

Section: Discussionmentioning

confidence: 99%

Having Children, Social Characteristics, Smoking and the Risk of Uveal Melanoma: A Case-Control Study

Zinkhan

Stang

Jöckel

et al. 2013

Ophthalmic Epidemiology

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The observed association between lower socioeconomic level and increased odds for uveal melanoma possibly represents a higher occupational uveal melanoma risk for occupational categories that are usually associated with lower socioeconomic status. Concerning having children and uveal melanoma development, we hypothesize that the observed association is mediated through alpha-melanocyte-stimulating hormone, a hormone that increases during pregnancy and is linked to pigmentation alterations in pregnant women.

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“…The methods varied slightly between the centers, and examples of methods can been found in Vajdic et al (32) and Kanetsky et al (33). We checked that the distribution of MC1R variants were in Hardy–Weinberg equilibrium; no departure from Hardy–Weinberg equilibrium at the 5% significance level was found.…”

Section: Methodsmentioning

confidence: 99%

Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study

Demenais¹,

Mohamdi²,

Chaudru³

et al. 2010

JNCI: Journal of the National Cancer Institute

113

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BackgroundCarrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.MethodsWe included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.ResultsCarrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).ConclusionResults show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.

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

Cited by 13 publications

References 24 publications

Role of MC1R variants in uveal melanoma

Role of MC1R variants in uveal melanoma

Having Children, Social Characteristics, Smoking and the Risk of Uveal Melanoma: A Case-Control Study

Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study

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