Skip to main content Accessibility help
×
Home
Hostname: page-component-747cfc64b6-nvdzj Total loading time: 0.389 Render date: 2021-06-12T14:25:59.056Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

Polymorphisms in Nevus-Associated Genes MTAP, PLA2G6, and IRF4 and the Risk of Invasive Cutaneous Melanoma

Published online by Cambridge University Press:  21 February 2012

Marina Kvaskoff
Affiliation:
Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), ‘Nutrition, Hormones, and Women's Health’ Team, Institut Gustave Roussy, Villejuif, France; Université Paris Sud 11, Villejuif, France; Queensland Institute of Medical Research, Brisbane, Australia.
David C. Whiteman
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Zhen Z. Zhao
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Grant W. Montgomery
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Nicholas G. Martin
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
Nicholas K. Hayward
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia.
David L. Duffy
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia. David.Duffy@qimr.edu.au
Corresponding
E-mail address:

Abstract

An evolving hypothesis postulates that melanomas may arise through ‘nevus-associated’ and ‘chronic sun exposure’ pathways. We explored this hypothesis by examining associations between nevus-associated loci and melanoma risk across strata of body site and histological subtype. We genotyped 1028 invasive case patients and 1469 controls for variants in methylthioadenosine phosphorylase (MTAP), phospholipase A2, group VI (PLA2G6), and Interferon regulatory factor 4 (IRF4), and compared allelic frequencies globally and by anatomical site and histological subtype of melanoma. Odds-ratios (ORs) and 95% confidence intervals (CIs) were calculated using classical and multinomial logistic regression models. Among controls, MTAP rs10757257, PLA2G6 rs132985 and IRF4 rs12203592 were the variants most significantly associated with number of nevi. In adjusted models, a significant association was found between MTAP rs10757257 and overall melanoma risk (OR = 1.32, 95% CI = 1.14–1.53), with no evidence of heterogeneity across sites (Phomogeneity =.52). In contrast, MTAP rs10757257 was associated with superficial spreading/nodular melanoma (OR = 1.34, 95% CI = 1.15– 1.57), but not with lentigo maligna melanoma (OR = 0.79, 95% CI = 0.46–1.35) (Phomogeneity =.06), the subtype associated with chronic sun exposure. Melanoma was significantly inversely associated with rs12203592 in children (OR = 0.35, 95% CI = 0.16–0.77) and adolescents (OR = 0.61, 95% CI = 0.42–0.91), but not in adults (Phomogeneity =.0008). Our results suggest that the relationship between MTAP and melanoma is subtype-specific, and that the association between IRF4 and melanoma is more evident for cases with a younger age at onset. These findings lend some support to the ‘divergent pathways’ hypothesis and may provide at least one candidate gene underlying this model. Further studies are warranted to confirm these findings and improve our understanding of these relationships.

Type
Articles
Copyright
Copyright © Cambridge University Press 2011
You have Access
33
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Polymorphisms in Nevus-Associated Genes MTAP, PLA2G6, and IRF4 and the Risk of Invasive Cutaneous Melanoma
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Polymorphisms in Nevus-Associated Genes MTAP, PLA2G6, and IRF4 and the Risk of Invasive Cutaneous Melanoma
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Polymorphisms in Nevus-Associated Genes MTAP, PLA2G6, and IRF4 and the Risk of Invasive Cutaneous Melanoma
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *