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Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families

Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, an...

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Autores principales: Liang, Xueying, Pfeiffer, Ruth M., Li, Wen-Qing, Brossard, Myriam, Burke, Laura S., Wheeler, William, Calista, Donato, Fargnoli, Maria Concetta, Ghiorzo, Paola, Peris, Ketty, Bianchi-Scarra’, Giovanna, Chaudru, Valerie, Zelenika, Diana, Maeder, Dennis, Burdette, Laurie, Yeager, Meredith, Chanock, Stephen, Landi, Maria Teresa, Demenais, Florence, Tucker, Margaret A., Goldstein, Alisa M., Yang, Xiaohong R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873368/
https://www.ncbi.nlm.nih.gov/pubmed/23892592
http://dx.doi.org/10.1038/jid.2013.316
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author Liang, Xueying
Pfeiffer, Ruth M.
Li, Wen-Qing
Brossard, Myriam
Burke, Laura S.
Wheeler, William
Calista, Donato
Fargnoli, Maria Concetta
Ghiorzo, Paola
Peris, Ketty
Bianchi-Scarra’, Giovanna
Chaudru, Valerie
Zelenika, Diana
Maeder, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Landi, Maria Teresa
Demenais, Florence
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
author_facet Liang, Xueying
Pfeiffer, Ruth M.
Li, Wen-Qing
Brossard, Myriam
Burke, Laura S.
Wheeler, William
Calista, Donato
Fargnoli, Maria Concetta
Ghiorzo, Paola
Peris, Ketty
Bianchi-Scarra’, Giovanna
Chaudru, Valerie
Zelenika, Diana
Maeder, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Landi, Maria Teresa
Demenais, Florence
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
author_sort Liang, Xueying
collection PubMed
description Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, and melanocyte proliferation pathways in a total of 504 individuals (310 with DN, 194 without DN) from 53 melanoma-prone families (23 CDKN2A mutation positive and 30 negative). Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each SNP separately, adjusted for age, sex, CMM and CDKN2A status. P-values for SNPs in the same gene were combined to yield gene-specific p-values. Two genes, CDK6 and XRCC1, were significantly associated with DN after Bonferroni correction for multiple testing (P=0.0001 and 0.00025, respectively), whereas neither gene was significantly associated with CMM. Associations for CDK6 SNPs were stronger in CDKN2A mutation positive families (rs2079147, P(interaction)=0.0033), whereas XRCC1 SNPs had similar effects in mutation-positive and negative families. The association for one of the associated SNPs in XRCC1 (rs25487) was replicated in two independent datasets (random effect meta-analysis: P<0.0001). Our findings suggest that some genetic variants may contribute to DN risk independently of their association with CMM in melanoma-prone families.
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spelling pubmed-38733682014-08-01 Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families Liang, Xueying Pfeiffer, Ruth M. Li, Wen-Qing Brossard, Myriam Burke, Laura S. Wheeler, William Calista, Donato Fargnoli, Maria Concetta Ghiorzo, Paola Peris, Ketty Bianchi-Scarra’, Giovanna Chaudru, Valerie Zelenika, Diana Maeder, Dennis Burdette, Laurie Yeager, Meredith Chanock, Stephen Landi, Maria Teresa Demenais, Florence Tucker, Margaret A. Goldstein, Alisa M. Yang, Xiaohong R. J Invest Dermatol Article Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, and melanocyte proliferation pathways in a total of 504 individuals (310 with DN, 194 without DN) from 53 melanoma-prone families (23 CDKN2A mutation positive and 30 negative). Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each SNP separately, adjusted for age, sex, CMM and CDKN2A status. P-values for SNPs in the same gene were combined to yield gene-specific p-values. Two genes, CDK6 and XRCC1, were significantly associated with DN after Bonferroni correction for multiple testing (P=0.0001 and 0.00025, respectively), whereas neither gene was significantly associated with CMM. Associations for CDK6 SNPs were stronger in CDKN2A mutation positive families (rs2079147, P(interaction)=0.0033), whereas XRCC1 SNPs had similar effects in mutation-positive and negative families. The association for one of the associated SNPs in XRCC1 (rs25487) was replicated in two independent datasets (random effect meta-analysis: P<0.0001). Our findings suggest that some genetic variants may contribute to DN risk independently of their association with CMM in melanoma-prone families. 2013-07-26 2014-02 /pmc/articles/PMC3873368/ /pubmed/23892592 http://dx.doi.org/10.1038/jid.2013.316 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Liang, Xueying
Pfeiffer, Ruth M.
Li, Wen-Qing
Brossard, Myriam
Burke, Laura S.
Wheeler, William
Calista, Donato
Fargnoli, Maria Concetta
Ghiorzo, Paola
Peris, Ketty
Bianchi-Scarra’, Giovanna
Chaudru, Valerie
Zelenika, Diana
Maeder, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Landi, Maria Teresa
Demenais, Florence
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title_full Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title_fullStr Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title_full_unstemmed Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title_short Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
title_sort association of genetic variants in cdk6 and xrcc1 with the risk of dysplastic nevi in melanoma-prone families
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873368/
https://www.ncbi.nlm.nih.gov/pubmed/23892592
http://dx.doi.org/10.1038/jid.2013.316
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