Melanocortin-1 receptor polymorphisms and risk of melanoma: Is the association explained solely by pigmentation phenotype?
Melanocortin-1 receptor polymorphisms and risk of melanoma: Is the association explained solely by pigmentation phenotype?
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DOI：
10.1086/302711
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发表时间：
2000-01-01
影响因子：
9.8
通讯作者：
Sturm, RA
中科院分区：
文献类型：
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作者：
Palmer, JS;Duffy, DL;Sturm, RA
皮肤恶性黑色素瘤（CMM）在阳光暴露的白人中风险增加，尤其是那些肤色较浅的人。本研究旨在探讨黑素皮质素 - 1受体（MC1R）基因型与CMM风险的关系，并控制色素沉着表型。我们报告了在澳大利亚一个基于人群的样本中，460例家族性和散发性CMM患者以及339例对照个体中五种常见MC1R变异体的出现情况，以及它们与皮肤、头发和眼睛颜色、雀斑和痣数量等其他风险因素的关系。MC1R变异体与头发颜色和皮肤类型之间有很强的关联。此外，在72%的CMM患者中发现了MC1R变异体，而只有56%的对照个体携带至少一种变异体（P <.001），这一发现与黑色素瘤家族史的强度无关。三个活性等位基因（Arg151Cys、Arg160Trp和Asp294His），先前与红头发有关，每多携带一个等位基因，CMM风险就增加一倍（比值比2.0；95%置信区间1.6 - 2.6）。Val60Leu和Asp84Glu变异体未显示出这种独立关联。仅在肤色较浅的个体中，CMM与MC1R变异体之间的这种关联不存在，但在那些报告为中等肤色或橄榄色/深色肤色的个体中仍然存在。我们得出结论，MC1R变异等位基因对CMM的影响部分是通过决定色素沉着表型来介导的，并且这些等位基因可能也抵消了该白人人群中一些成员通常因较深肤色而具有的保护作用。
Risk of cutaneous malignant melanoma (CMM) is increased in sun-exposed whites, particularly those with a pale complexion. This study was designed to investigate the relationship of the melanocortin-1 receptor (MC1R) genotype to CMM risk, controlled for pigmentation phenotype. We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 339 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count. There was a strong relationship between MC1R variants and hair color and skin type. Moreover, MC1R variants were found in 72% of the individuals with CMM, whereas only 56% of the control individuals carried at least one variant (P < .001), a finding independent of strength of family history of melanoma. Three active alleles (Arg151Cys, Arg160Trp, and Asp294His), previously associated with red hair, doubled CMM risk for each additional allele carried (odds ratio 2.0; 95% confidence interval 1.6-2.6). No such independent association could be demonstrated with the Val60Leu and Asp84Glu variants. Among pale-skinned individuals alone, this association between CMM and MC1R variants was absent, but it persisted among those reporting a medium or olive/dark complexion. We conclude that the effect that MC1R variant alleles have on CMM is partly mediated via determination of pigmentation phenotype and that these alleles may also negate the protection normally afforded by darker skin coloring in some members of this white population.