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Melanoma susceptibility variant rs869330 in the MTAP gene is associated with melanoma outcome

Marasigan, Viviena,,*; Güvenç, Canana,,*; van den Oord, Joost J.b; Stas, Margueritec; Boecxstaens, Veerlec; Bechter, Oliverd; Wolter, Pascalg; Lambrechts, Diethere,,f; Garmyn, Marjana

doi: 10.1097/CMR.0000000000000578
Original Articles: Translational Research
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The rising incidence of cutaneous melanoma (CM), an aggressive skin cancer, emphasizes the need for novel biomarkers to guide personalized care and better predict outcome. Genetic factors including germline risk variants are promising candidates for this aim. We explored the association between germline risk variants and melanoma outcome in a large genetically homogenous Belgian melanoma population, focusing on single nucleotide polymorphisms which generated the highest association with melanoma susceptibility. Between 2004 and 2014, blood samples of 1088 patients with histologically confirmed CM were collected and genotyped for nine variants. Cox proportional hazard models were used to assess the association between each single nucleotide polymorphism and relapse-free survival and overall survival, adjusted by age, sex, melanoma stage, site, and subtype. We identified significant associations for rs869330 (in the methylthioadenosine phosphorylase – MTAP gene) with overall survival (hazard ratio = 0.760, P = 0.048, 95% confidence interval: 0.580–0.998) and relapse-free survival (hazard ratio = 0.800, P = 0.020, 95% confidence interval: 0.650–0.970). This exploratory study is the first to show a significant association between the rs869330 variant (in the MTAP gene) and outcome in a large CM population.

Departments of aDermatology

bImaging and Pathology, Translational Cell and Tissue Research

cSurgical Oncology

dGeneral Medical Oncology, University Hospitals Leuven

eVIB Center for Cancer Biology, VIB

fLaboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven

gDepartment of Hematology and Oncology, CHR Verviers East, Verviers, Belgium

* Vivien Marasigan and Canan Güvenç contributed equally to the writing of this article.

Received 25 September 2018 Accepted 26 December 2018

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.melanomaresearch.com.

Correspondence to Marjan Garmyn, PhD, MD, Department of Dermatology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium Tel: +32 16 337 950; fax: +32 16 337 951; e-mail: marjan.garmyn@uzleuven.be

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