Suppr超能文献

黑素皮质素-1受体基因多态性与黑色素瘤风险:这种关联是否仅由色素沉着表型所解释?

Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?

作者信息

Palmer J S, Duffy D L, Box N F, Aitken J F, O'Gorman L E, Green A C, Hayward N K, Martin N G, Sturm R A

机构信息

Centre for Molecular and Cellular Biology and Queensland Institute of Medical Research and Joint Genetics Program, University of Queensland, Brisbane, QLD 4072, Australia.

出版信息

Am J Hum Genet. 2000 Jan;66(1):176-86. doi: 10.1086/302711.

Abstract

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 399 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.

摘要

皮肤暴露于阳光下的白人,尤其是肤色苍白者,患皮肤恶性黑色素瘤(CMM)的风险会增加。本研究旨在探讨黑素皮质素-1受体(MC1R)基因型与CMM风险之间的关系,并对色素沉着表型进行控制。我们报告了在一个基于澳大利亚人群的样本中,460名患有家族性和散发性CMM的个体以及399名对照个体中5种常见MC1R变异的发生情况,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变异与头发颜色和皮肤类型之间存在密切关系。此外,72%的CMM患者存在MC1R变异,而只有56%的对照个体携带至少一种变异(P<0.001),这一发现与黑色素瘤家族史的强度无关。先前与红发相关的3个活性等位基因(Arg151Cys、Arg160Trp和Asp294His),每多携带一个等位基因,CMM风险就会增加一倍(优势比2.0;95%置信区间1.6 - 2.6)。Val60Leu和Asp84Glu变异未显示出这种独立关联。仅在肤色苍白的个体中,CMM与MC1R变异之间不存在这种关联,但在报告中等或橄榄色/深色肤色的个体中这种关联仍然存在。我们得出结论,MC1R变异等位基因对CMM的影响部分是通过色素沉着表型的决定来介导的,并且这些等位基因可能也会抵消该白人人群中某些成员通常由较深肤色提供的保护作用。

相似文献

4
Interactive effects of MC1R and OCA2 on melanoma risk phenotypes.
Hum Mol Genet. 2004 Feb 15;13(4):447-61. doi: 10.1093/hmg/ddh043. Epub 2004 Jan 6.
5
Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma.
J Invest Dermatol. 2001 Feb;116(2):224-9. doi: 10.1046/j.1523-1747.2001.01224.x.
6
High naevus count and MC1R red hair alleles contribute synergistically to increased melanoma risk.
Br J Dermatol. 2019 Nov;181(5):1009-1016. doi: 10.1111/bjd.17833. Epub 2019 Jul 17.
7
Melanocortin 1 receptor variants in an Irish population.
J Invest Dermatol. 1998 Jul;111(1):119-22. doi: 10.1046/j.1523-1747.1998.00252.x.
9
The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes.
Pigment Cell Res. 2003 Jun;16(3):266-72. doi: 10.1034/j.1600-0749.2003.00041.x.
10
Genetic studies of the human melanocortin-1 receptor.
Ann N Y Acad Sci. 1999 Oct 20;885:134-42. doi: 10.1111/j.1749-6632.1999.tb08670.x.

引用本文的文献

1
Assessing MC1R Variants in Lentigo Maligna Melanoma within the Utah Population.
Cancer Res Commun. 2025 Jul 1;5(7):1228-1234. doi: 10.1158/2767-9764.CRC-25-0263.
3
Research Progress of GPR137 in Malignant Tumors: A Review.
Onco Targets Ther. 2025 Apr 15;18:545-558. doi: 10.2147/OTT.S511943. eCollection 2025.
5
Melanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia.
PLoS Biol. 2024 Dec 2;22(12):e3002940. doi: 10.1371/journal.pbio.3002940. eCollection 2024 Dec.
6
An overview of benefits and risks of chronic melanocortin-1 receptor activation.
J Eur Acad Dermatol Venereol. 2025 Jan;39(1):39-51. doi: 10.1111/jdv.20269. Epub 2024 Jul 31.
7
Forensic DNA Phenotyping: Genes and Genetic Variants for Eye Color Prediction.
Genes (Basel). 2023 Aug 10;14(8):1604. doi: 10.3390/genes14081604.
8
Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma.
J Transl Med. 2023 Aug 22;21(1):562. doi: 10.1186/s12967-023-04405-y.
9
10
Cutaneous Melanoma and Glioblastoma Multiforme Association-Case Presentation and Literature Review.
Diagnostics (Basel). 2023 Mar 9;13(6):1046. doi: 10.3390/diagnostics13061046.

本文引用的文献

2
Skin type, melanoma, and melanocortin 1 receptor variants.
J Invest Dermatol. 1999 Apr;112(4):512-3. doi: 10.1046/j.1523-1747.1999.00554.x.
3
CDKN2A variants in a population-based sample of Queensland families with melanoma.
J Natl Cancer Inst. 1999 Mar 3;91(5):446-52. doi: 10.1093/jnci/91.5.446.
4
Human pigmentation genes and their response to solar UV radiation.
Mutat Res. 1998 Nov 9;422(1):69-76. doi: 10.1016/s0027-5107(98)00176-6.
5
Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins.
Genet Epidemiol. 1999;16(1):40-53. doi: 10.1002/(SICI)1098-2272(1999)16:1<40::AID-GEPI4>3.0.CO;2-1.
6
Human pigmentation genetics: the difference is only skin deep.
Bioessays. 1998 Sep;20(9):712-21. doi: 10.1002/(SICI)1521-1878(199809)20:9<712::AID-BIES4>3.0.CO;2-I.
7
p53 expression and risk factors for cutaneous melanoma: a case-control study.
Int J Cancer. 1998 Sep 11;77(6):843-8. doi: 10.1002/(sici)1097-0215(19980911)77:6<843::aid-ijc8>3.0.co;2-u.
8
Iris color, skin sun sensitivity, and age-related maculopathy. The Blue Mountains Eye Study.
Ophthalmology. 1998 Aug;105(8):1359-63. doi: 10.1016/S0161-6420(98)98013-7.
9
Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene.
J Invest Dermatol. 1998 Aug;111(2):218-21. doi: 10.1046/j.1523-1747.1998.00287.x.
10
Melanocortin 1 receptor variants in an Irish population.
J Invest Dermatol. 1998 Jul;111(1):119-22. doi: 10.1046/j.1523-1747.1998.00252.x.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验