MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population
MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population
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DOI：
10.1093/jnci/dji176
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发表时间：
2005-07-06
期刊：
影响因子：
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通讯作者：
Pfeiffer, RM
中科院分区：
文献类型：
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作者：
Landi, MT;Kanetsky, PA;Pfeiffer, RM
背景。黑色素瘤的风险因素包括白皙的肤色、多发痣、DNA修复能力低以及CDKN2A或CDK4突变。黑素皮质素 - 1受体（MCIR）基因的变异与白皙肤色和黑色素瘤风险相关，刺鼠信号蛋白（ASIP）基因的多态性与深色肤色相关。我们在地中海人群中研究了MCIR和ASIP基因型与表型特征、散发性和家族性黑色素瘤风险以及作为疾病进展指标的黑色素瘤厚度的关系。
方法：我们对来自意大利东北部一项病例对照研究和一项家族研究的267名黑色素瘤患者和382名对照受试者进行了研究。通过体格检查、问卷调查、分光光度计和最小红斑量测量来评估宿主因素。对MC1R进行测序，对ASIP进行基因分型，并通过宿主细胞再激活试验测量DNA修复能力。通过逻辑回归模型估计比值比（ORs）和95%置信区间（CIs）。还评估了表型特征和DNA修复能力对MCIR与黑色素瘤风险之间关联的影响修饰。所有统计检验均为双侧检验。
结果：与携带野生型MCIR相比，携带MCIR变异等位基因使散发性和家族性黑色素瘤的风险增加2 - 4倍，特别是在携带多个变异等位基因的个体中（OR 3.9；95% CI = 3.3 - 4.6）。在其他风险因素较少（皮肤黝黑或痣少）的个体中，这种关联更强。MC1R变异等位基因携带者患厚黑色素瘤的可能性也比非携带者高3 - 4倍。ASIP多态性与肤色、痣或黑色素瘤风险无关。
结论：在地中海人群中，MCIR与黑色素瘤风险和进展相关，特别是在没有其他强风险因素（如雀斑或多发痣）的情况下。
Background. Melanoma risk factors include fair pigmentation, multiple nevi, low DNA repair capacity, and CDKN2A or CDK4 mutations. Variants of the melanocortin-1 receptor (MCIR) gene have been associated with fair pigmentation and melanoma risk, and a polymorphism of the Agouti Signaling Protein (ASIP) gene has been associated with dark pigmentation. We examined MCIR and ASIP genotypes in relation to phenotypic characteristics, sporadic and familial melanoma risk, and melanoma thickness as an indicator of disease progression in a Mediterranean population. Methods: We studied 267 melanoma patients and 382 control subjects from a case-control study and a family study in northeastern Italy. Host factors were assessed by physical examination, questionnaire, spectrophotometer, and minimal erythema dose measurement. MC1R was sequenced, ASIP was genotyped, and DNA repair capacity was measured by the host-cell reactivation assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Effect modification of the association between MCIR and melanoma risk by phenotypic characteristics and DNA repair capacity was also assessed. All statistical tests were two-sided. Results: Carrying MCIR variant alleles was associated with a two- to fourfold increase in risk of both sporadic and familial melanoma compared with carrying wild-type MCIR, particularly in individuals carrying multiple variant alleles (OR 3.9; 95% CI = 3.3 to 4.6). This association was stronger in individuals with fewer additional risk factors (those with dark skin or few nevi). MC1R variant allele carriers were also three to four times more likely than were non-carriers to have thick melanomas. The ASIP polymorphism was not associated with pigmentation, nevi, or melanoma risk. Conclusions: MCIR was associated with melanoma risk and progression in a Mediterranean population, particularly in the absence of other strong risk factors, such as freckling or many nevi.