TY - JOUR
T1 - Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families
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.
PY - 2014/2
Y1 - 2014/2
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
AB - 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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U2 - 10.1038/jid.2013.316
DO - 10.1038/jid.2013.316
M3 - Article
C2 - 23892592
AN - SCOPUS:84892821254
VL - 134
SP - 481
EP - 487
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 2
ER -