Influence of genetic variants in type I interferon genes on melanoma survival and therapy.

Melanoma is an immunogenic tumor; however, the efficacy of immune-therapy shows large inter-individual variation with possible influence of background genetic variation. In this study we report the influence of genetic polymorphisms in the type I interferon gene cluster on chromosome 9p22 on melanom...

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Autores principales:	Romina Elizabeth Lenci, Melanie Bevier, Andreas Brandt, Justo Lorenzo Bermejo, Antje Sucker, Iris Moll, Dolores Planelles, Celia Requena, Eduardo Nagore, Kari Hemminki, Dirk Schadendorf, Rajiv Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db5682c8bc814c1e90cbaba79b51cd69
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spelling	oai:doaj.org-article:db5682c8bc814c1e90cbaba79b51cd692021-11-18T08:07:21ZInfluence of genetic variants in type I interferon genes on melanoma survival and therapy.1932-620310.1371/journal.pone.0050692https://doaj.org/article/db5682c8bc814c1e90cbaba79b51cd692012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23209811/?tool=EBIhttps://doaj.org/toc/1932-6203Melanoma is an immunogenic tumor; however, the efficacy of immune-therapy shows large inter-individual variation with possible influence of background genetic variation. In this study we report the influence of genetic polymorphisms in the type I interferon gene cluster on chromosome 9p22 on melanoma survival. We genotyped 625 melanoma patients recruited in an oncology center in Germany for 44 polymorphisms located on chromosome 9p22 that were informative for 299 polymorphisms and spanned 15 type I interferon genes. Our results showed associations between time to metastasis/survival and two linked (r(2) = 0.76) polymorphisms, rs10964859 (C>G) and rs10964862 (C>A). The rs10964859 polymorphism was located at 3'UTR and rs10964862 was 9.40 Kb towards 5'UTR of IFNW1 gene. The carriers of the variant alleles of the rs10964859 and rs10964862 polymorphisms were associated with a reduced disease-free survival. The validation of data in an independent group of 710 patients from Spain showed that the direction of the effect was similar. Stratification based on therapy showed that the adverse effect on metastasis development was statistically significant in the patients from Spain who did not receive any treatment and were homozygous for variant allele of rs10964862 (HR = 2.52, 95% CI 1.07-5.90; P = 0.03). Patients homozygous for rs10964859 (HR = 2.01, 95% CI 1.17-3.44; P = 0.01) and rs10964862 (HR 1.84, 95%CI 1.03-3.27, P = 0.04) were associated to increased risk of death following metastasis. GTCGACAA haplotype, found in 8.8% of the patients, was associated with an increased risk of death (HR 1.94, 95%CI 1.16-3.26, P = 0.01). In conclusion, our results identified genetic variants in interferon genes that influence melanoma progression and survival with modulation of effect due to treatment status.Romina Elizabeth LenciMelanie BevierAndreas BrandtJusto Lorenzo BermejoAntje SuckerIris MollDolores PlanellesCelia RequenaEduardo NagoreKari HemminkiDirk SchadendorfRajiv KumarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50692 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Romina Elizabeth Lenci Melanie Bevier Andreas Brandt Justo Lorenzo Bermejo Antje Sucker Iris Moll Dolores Planelles Celia Requena Eduardo Nagore Kari Hemminki Dirk Schadendorf Rajiv Kumar Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
description	Melanoma is an immunogenic tumor; however, the efficacy of immune-therapy shows large inter-individual variation with possible influence of background genetic variation. In this study we report the influence of genetic polymorphisms in the type I interferon gene cluster on chromosome 9p22 on melanoma survival. We genotyped 625 melanoma patients recruited in an oncology center in Germany for 44 polymorphisms located on chromosome 9p22 that were informative for 299 polymorphisms and spanned 15 type I interferon genes. Our results showed associations between time to metastasis/survival and two linked (r(2) = 0.76) polymorphisms, rs10964859 (C>G) and rs10964862 (C>A). The rs10964859 polymorphism was located at 3'UTR and rs10964862 was 9.40 Kb towards 5'UTR of IFNW1 gene. The carriers of the variant alleles of the rs10964859 and rs10964862 polymorphisms were associated with a reduced disease-free survival. The validation of data in an independent group of 710 patients from Spain showed that the direction of the effect was similar. Stratification based on therapy showed that the adverse effect on metastasis development was statistically significant in the patients from Spain who did not receive any treatment and were homozygous for variant allele of rs10964862 (HR = 2.52, 95% CI 1.07-5.90; P = 0.03). Patients homozygous for rs10964859 (HR = 2.01, 95% CI 1.17-3.44; P = 0.01) and rs10964862 (HR 1.84, 95%CI 1.03-3.27, P = 0.04) were associated to increased risk of death following metastasis. GTCGACAA haplotype, found in 8.8% of the patients, was associated with an increased risk of death (HR 1.94, 95%CI 1.16-3.26, P = 0.01). In conclusion, our results identified genetic variants in interferon genes that influence melanoma progression and survival with modulation of effect due to treatment status.
format	article
author	Romina Elizabeth Lenci Melanie Bevier Andreas Brandt Justo Lorenzo Bermejo Antje Sucker Iris Moll Dolores Planelles Celia Requena Eduardo Nagore Kari Hemminki Dirk Schadendorf Rajiv Kumar
author_facet	Romina Elizabeth Lenci Melanie Bevier Andreas Brandt Justo Lorenzo Bermejo Antje Sucker Iris Moll Dolores Planelles Celia Requena Eduardo Nagore Kari Hemminki Dirk Schadendorf Rajiv Kumar
author_sort	Romina Elizabeth Lenci
title	Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
title_short	Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
title_full	Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
title_fullStr	Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
title_full_unstemmed	Influence of genetic variants in type I interferon genes on melanoma survival and therapy.
title_sort	influence of genetic variants in type i interferon genes on melanoma survival and therapy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/db5682c8bc814c1e90cbaba79b51cd69
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Influence of genetic variants in type I interferon genes on melanoma survival and therapy.

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