Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations

被引：35

作者：

Yang, Xiaohong Rose ^{[1
,2
]}

Liang, Xueying ^{[2
]}

Pfeiffer, Ruth M. ^{[2
]}

Wheeler, William ^{[3
]}

Maeder, Dennis ^{[2
]}

Burdette, Laurie ^{[4
]}

Yeager, Meredith ^{[4
]}

Chanock, Stephen ^{[2
]}

Tucker, Margaret A. ^{[2
]}

Goldstein, Alisa M. ^{[2
]}

机构：

[1] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA

[2] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA

[3] Informat Management Serv Inc, Rockville, MD USA

[4] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA

来源：

FAMILIAL CANCER | 2010年 / 9卷 / 04期

关键词：

Melanoma; Nevi; Chromosome; 9p21; SNP; CDKN2A; METHYLTHIOADENOSINE PHOSPHORYLASE GENE; GENOME-WIDE ASSOCIATION; IRON-REGULATORY GENES; GERM-LINE MUTATIONS; RISK; POLYMORPHISMS; LINKAGE; CANCER; EXPRESSION; OVEREXPRESSION;

D O I：

10.1007/s10689-010-9356-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chromosome 9p21 has been implicated in the pathogenesis of cutaneous malignant melanoma (CMM). In addition to CDKN2A, the major known high-risk susceptibility gene for CMM, recent studies suggest that other 9p21 genes may be involved in melanoma/nevi development. To identify 9p21 variants that influence susceptibility to CMM and number of nevi in CMM-prone families with and without CDKN2A mutations, we analyzed 562 individuals (183 CMM) from 53 families (23 CDKN2A+, 30 CDKN2A-) for 233 tagging SNPs in 21 genes at 9p21. Single SNP- and gene-based regression analyses were used to assess the risk of CMM, nevi count, skin complexion, and tanning ability associated with these SNPs and genes. We found that SNP rs7023329 in the MTAP gene was associated with number of nevi (P (trend) = 0.003) confirming a recent finding by a genome-wide association study. In addition, three SNPs in the ACO1 gene, rs7855483 (P (trend) = 0.002), rs17288067 (P (trend) = 0.0009), and rs10813813 (P (trend) = 0.005), showed the strongest associations with CMM risk. None of the examined 9p21 SNPs was associated with skin complexion, whereas two SNPs, rs10964862 in IFNW1 (P (trend) = 0.003), and rs13290968 in TUSC1 (P (trend) = 0.0006), were associated with tanning ability. Gene-based analyses suggested that the ACO1 gene was significantly associated with CMM (P = 0.0004); genes IFNW1 (P = 0.002) and ACO1 (P = 0.0002) were significantly associated with tanning ability. Our findings are consistent with recent proposals that additional 9p21 genes may contribute to CMM susceptibility in CMM-prone families. These genetic variants may, at least partially, exert their effects through nevi and tanning ability.

引用

页码：625 / 633

页数：9