Functional analysis of human MC1R polymorphisms in directing melanocyte phenotype

人类MC1R多态性在指导黑素细胞表型中的功能分析

• 批准号: nhmrc : 142988
• 负责人: A/Pr Neil Box
• 金额: $ 24.11万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-analysis-human-melanocyte-phenotype/96206
• 关键词: Functional; analysis; human; MC1R; polymorphisms

Sunsmart campaigns are a unifying element in the lives of many Australians who wish to ensure protection against the damaging effects of ultraviolet rays in sunlight. Indeed, Australians have the highest incidence of UV-induced melanoma in the world. Although it is evident that lighter skin colours are more susceptible to sun damage, the relationship between sun exposure, skin type and melanoma formation is less clear. An essential first step in understanding the complex interactions that give rise to melanoma, and in identifying individuals that have a high susceptibility, is to reduce phenotypic analyses to genotypic classifications. As pigmentation phenotype is a factor of central importance in determining an individuals risk for melanoma, characterisation of the genes underlying the physical qualities of human eye, hair and skin colour will give a more direct and accurate genotypic assessment of risk. Results from an epidemiology study of melanoma patients in Queensland have identified a number of genetic changes within the melanocyte stimulating hormone receptor (MC1R) gene that associate with skin, hair and eye colour as well as with incidence of melanoma. Further investigation of MC1R gene alleles which segregate with skin and hair colours will provide the beginning for a whole new genotype-based classification of skin colour and melanoma risk, and will significantly contribute to our understanding of what makes some individuals highly susceptible to melanoma while others are not. Indeed, MC1R polymorphisms may numerically be the most important melanoma predisposition gene yet identified, exerting its effects as one of those common genes of small effect which may account for much more of the case load in melanoma than rarer genes of large effect. Studies such as this will enable powerful genotyping methods to be employed in identification of those individuals at highest risk for melanoma and other skin cancers.

SunSmart活动是许多澳大利亚人生活中的一个统一元素，他们希望确保免受阳光中紫外线的破坏影响。事实上，澳大利亚人的紫外线黑色素瘤发病率是世界上最高的。尽管浅色皮肤显然更容易受到日晒损伤，但日晒、皮肤类型和黑色素瘤形成之间的关系还不是很清楚。要了解导致黑色素瘤的复杂相互作用，并识别具有高易感性的个体，关键的第一步是将表型分析减少到基因类型分类。由于色素沉着表型是确定个人患黑色素瘤风险的核心重要因素，对人类眼睛、头发和皮肤颜色的生理特征进行基因表征将给出更直接和准确的风险基因评估。昆士兰州一项对黑色素瘤患者的流行病学研究结果发现，黑素细胞刺激素受体(MC1R)基因中的许多基因变化与皮肤、头发和眼睛的颜色以及黑色素瘤的发病率有关。对MC1R基因等位基因的进一步研究将为一种全新的基于基因的肤色和黑色素瘤风险分类提供开始，并将大大有助于我们理解是什么使一些人对黑色素瘤高度易感，而另一些人则不是。事实上，MC1R基因的多态在数值上可能是迄今发现的最重要的黑色素瘤易感基因，其作用是作为一种常见的小效应基因，可能比罕见的大效应基因更能解释黑色素瘤的发病情况。这样的研究将使强大的基因分型方法被用于识别那些黑色素瘤和其他皮肤癌风险最高的人。