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

Xueying Liang, Ruth M. Pfeiffer, Wen Qing Li, Myriam Brossard, Laura S. Burke, William Wheeler, Donato Calista, Maria Concetta Fargnoli, Paola Ghiorzo, Ketty Peris, Giovanna Bianchi-Scarra, Valerie Chaudru, Diana Zelenika, Dennis Maeder, Laurie Burdette, Meredith Yeager, Stephen Chanock, Maria Teresa Landi, Florence Demenais, Margaret A. TuckerAlisa M. Goldstein, Xiaohong R. Yang

Research output: Contribution to journalArticle

Abstract

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 single-nucleotide polymorphism (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 (cyclin-dependent kinase 6) 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 data sets (random-effect meta-analysis: P

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalJournal of Investigative Dermatology
Volume134
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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Cyclin-Dependent Kinase 6
Dysplastic Nevus Syndrome
Nevi and Melanomas
Genes
Single Nucleotide Polymorphism
Mutation
Melanoma
Polymorphism
Melanocytes
Pigmentation
Logistics
Cell Cycle Checkpoints
Repair
DNA Repair
Nucleotides
Cells
Meta-Analysis
Logistic Models
DNA
Testing

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Liang, X., Pfeiffer, R. M., Li, W. Q., Brossard, M., Burke, L. S., Wheeler, W., ... Yang, X. R. (2014). Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families. Journal of Investigative Dermatology, 134(2), 481-487. https://doi.org/10.1038/jid.2013.316

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.

In: Journal of Investigative Dermatology, Vol. 134, No. 2, 02.2014, p. 481-487.

Research output: Contribution to journalArticle

Liang, X, Pfeiffer, RM, Li, WQ, Brossard, M, Burke, LS, Wheeler, W, Calista, D, Fargnoli, MC, Ghiorzo, P, Peris, K, Bianchi-Scarra, G, Chaudru, V, Zelenika, D, Maeder, D, Burdette, L, Yeager, M, Chanock, S, Landi, MT, Demenais, F, Tucker, MA, Goldstein, AM & Yang, XR 2014, 'Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families', Journal of Investigative Dermatology, vol. 134, no. 2, pp. 481-487. https://doi.org/10.1038/jid.2013.316
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. In: Journal of Investigative Dermatology. 2014 ; Vol. 134, No. 2. pp. 481-487.
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AU - Liang, Xueying

AU - Pfeiffer, Ruth M.

AU - Li, Wen Qing

AU - Brossard, Myriam

AU - Burke, Laura S.

AU - Wheeler, William

AU - Calista, Donato

AU - Fargnoli, Maria Concetta

AU - Ghiorzo, Paola

AU - Peris, Ketty

AU - Bianchi-Scarra, Giovanna

AU - Chaudru, Valerie

AU - Zelenika, Diana

AU - Maeder, Dennis

AU - Burdette, Laurie

AU - Yeager, Meredith

AU - Chanock, Stephen

AU - Landi, Maria Teresa

AU - Demenais, Florence

AU - Tucker, Margaret A.

AU - Goldstein, Alisa M.

AU - Yang, Xiaohong R.

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N2 - 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 single-nucleotide polymorphism (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 (cyclin-dependent kinase 6) 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 data sets (random-effect meta-analysis: P

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