Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations
Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations
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DOI：
10.1158/1055-9965.epi-05-0321
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发表时间：
2005-09-01
影响因子：
3.8
通讯作者：
Tucker, MA
中科院分区：
文献类型：
--
作者：
Goldstein, AM;Landi, MT;Tucker, MA
黑色素瘤的主要危险因素包括许多痣，特别是发育不良痣、色素沉着、雀斑、晒黑能力差以及CDKN2A、CDK4或MC1R基因的种系突变。我们利用广泛的临床和流行病学数据评估了CDKN2A黑色素瘤易发家族中MC1R与黑色素瘤风险之间的关系。我们研究了来自16个美国CDKN2A家族的395名受试者。通过临床检查或问卷调查评估黑色素瘤的主要危险因素；对MC1R进行测序。比值比通过无条件和条件逻辑回归模型估计。我们研究了多发性原发性黑色素瘤（MPM）和单发原发性黑色素瘤（SPM）患者中MC1R变异的分布和黑色素瘤诊断时的中位年龄。存在多种MC1R变异与黑色素瘤显著相关，即使在调整了主要的黑色素瘤危险因素后也是如此。所有40例MPM患者至少有一种MC1R变异；65%的MPM患者有至少两种MC1R变异，而只有17%的SPM患者有至少两种MC1R变异（P < 0.0001）。对于所有69例黑色素瘤患者和40例MPM患者，随着MCIR变异数量的增加，诊断时的中位年龄有统计学意义上的显著下降（P = 0.010和P = 0.008分别）。相比之下，SPM患者在黑色素瘤诊断时的年龄没有显著降低（P = 0.91）。目前的研究表明，多种MCIR变异的存在与CDKN2A突变患者的多发性黑色素瘤的发展有关。需要进一步的研究来证实这些发现，并探索可能促成这种关系的机制。
Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P < 0.0001). For all 69 melanoma patients combined, as well as the 40 MPM patients, there was a statistically significant decrease in median age at diagnosis as numbers of MCIR variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MCIR variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship.