Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color
Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color
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DOI：
10.1046/j.0022-202x.2001.01421.x
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发表时间：
2001-08-01
影响因子：
6.5
通讯作者：
Bavinck, JNB
中科院分区：
文献类型：
--
作者：
Kennedy, C;ter Huurne, J;Bavinck, JNB
携带黑皮质素1受体基因变异的个体发生皮肤黑色素瘤的风险增加。黑皮质素1受体基因变异也与黑色素瘤的其他风险因素有关，如白皙的皮肤和红色的头发。我们在123例皮肤黑色素瘤患者和385例对照组中评估了黑皮质素1受体基因变异、白皙皮肤、红发与黑色素瘤发生的关系。为了分析黑皮质素1受体基因变异与皮肤类型或发色之间的关系，我们还利用了453例非黑色素瘤皮肤癌患者。我们分析了黑皮质素1受体基因区的编码序列的单链构象多态性分析，然后通过DNA序列分析。黑色素瘤的风险依赖于各种黑皮质素1受体变异等位基因的暴露比值比估计。对所有不同的黑皮质素1受体基因变异的分析表明，黑皮质素1受体基因变异的存在相当于更高的黑色素瘤风险，在分层分析中，这与皮肤类型和头发颜色无关。根据皮肤类型调整后，两种变体的比值比分别为3.6（95% CI 1.7-7.2），一种变体为2.7（95% CI 1.5-5.1）。Va 160 Leu、Va 192 Met、Arg 142 His、Arg 151 Cys、Arg 160 Trp、Arg 163 Gln和His 260 Pro变异的复合杂合子和纯合子患黑色素瘤的优势比约为4，而这些变异的杂合子患黑色素瘤的风险为一半。在复合杂合子和杂合子中，黑皮质素1受体基因变异体Asp 84 Glu的存在似乎对皮肤黑色素瘤的风险最高，比值比分别为16.1（95%CI 2.3-139.0）和8.1（95%CI 1.2-55.9）。然而，当单独分析不同的变体时，广泛的置信区间不允许得出关于这些风险的大小的明确结论。在更常见的黑皮质素1受体变体等位基因Asp 84 Glu、Arg 142 His、Arg 151 Cys、Arg 160 Trp、His 260 Pro和Asp 294 His变体中，与白皙皮肤和红色头发都密切相关。然而，Va 160 Leu、Va 192 Met和Arg 163 Gln变异等位基因仅与白皙皮肤类型和/或红发弱相关或不相关，这进一步说明了皮肤类型、发色和黑色素瘤是黑皮质素1受体基因变异存在的独立结果。我们的结论是，许多黑皮质素1受体变异体易患皮肤黑色素瘤，Asp 84 Glu变异体可能赋予最高的风险。这种倾向在很大程度上与皮肤类型和头发颜色无关。
Individuals carrying melanocortin 1 receptor gene variants have an increased risk for the development of cutaneous melanoma. Melanocortin 1 receptor gene variants are also associated with other risk factors for melanoma such as fair skin and red hair. We evaluated the relationship of melanocortin 1 receptor gene variants, fair skin, red hair and the development of melanoma in 123 patients with cutaneous melanoma and 385 control subjects. To analyze the association between melanocortin 1 receptor gene variants and skin type or hair color we also made use of 453 patients with nonmelanoma skin cancer. We analyzed the coding sequence of the melanocortin 1 receptor gene region by single-stranded conformation polymorphism analysis, followed by DNA sequence analysis. Risk of melanoma dependent on the various melanocortin 1 receptor variant alleles was estimated by exposure odds ratios. The analyses of all different melanocortin 1 receptor gene variants combined, showed that the presence of melanocortin 1 receptor gene variants amounted to a higher melanoma risk, which, in stratified analyses, was independent of skin type and hair color. The odds ratios after adjusting for skin type were 3.6 (95% CI 1.7-7.2) for two variants and 2.7 (95% CI 1.5-5.1) for one variant, respectively. Compound heterozygotes and homozygotes for the Va160Leu, Va192Met, Arg142His, Arg151Cys, Arg160Trp, Arg163Gln, and His260Pro variants had odds ratios of about 4 to develop melanoma, whereas heterozygotes for these variants had half the risk. The presence of the melanocortin 1 receptor gene variant Asp84Glu appeared to impose the highest risk for cutaneous melanoma with odds ratios of 16.1 (95% CI 2.3-139.0) and 8.1 (95% CI 1.2-55.9) in compound heterozygotes and heterozygotes, respectively. The broad confidence intervals, when the different variants were analyzed separately, however, do not allow drawing definite conclusions about the magnitude of these risks. Of the more frequently occurring melanocortin 1 receptor variant alleles the Asp84Glu, Arg142His, Arg151Cys, Arg160Trp, His260Pro, and Asp294His variants were strongly associated with both fair skin and red hair. The Va160Leu, Va192Met, and Arg163Gln variant alleles, however, were only weakly or not associated with fair skin type and/or red hair, which further illustrates the finding that skin type, hair color, and melanoma are independent outcomes of the presence of melanocortin 1 receptor gene variants. We conclude that numerous melanocortin 1 receptor variants predispose to cutaneous melanoma and that possibly the Asp84Glu variant confers the highest risk. This predisposition is largely independent of skin type and hair color.