Functional analysis of human MC1R polymorphisms in directing melanocyte phenotype

Sunsmart运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性影响。事实上，澳大利亚人是世界上紫外线诱发黑色素瘤发病率最高的国家。虽然很明显，较浅的肤色更容易受到阳光的伤害，但阳光照射，皮肤类型和黑色素瘤形成之间的关系尚不清楚。在理解引起黑色素瘤的复杂相互作用和识别具有高易感性的个体中，重要的第一步是将表型分析减少到基因型分类。由于色素沉着表型是决定个体患黑色素瘤风险的重要因素，因此表征人眼、头发和皮肤颜色的物理特性的基因将提供更直接和准确的风险基因型评估。来自昆士兰州黑色素瘤患者的流行病学研究结果已经确定了黑色素细胞刺激激素受体（MC1 R）基因内的许多遗传变化，这些变化与皮肤、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肤色和黑色素瘤风险的全新基因型分类提供开端，并将大大有助于我们了解是什么使一些人对黑色素瘤高度易感，而另一些人则不然。事实上，MC1R多态性可能在数字上是最重要的黑色素瘤易感基因尚未确定，发挥其作用，作为那些常见的基因之一，小的影响，这可能占更多的情况下负荷在黑色素瘤比罕见的基因大的影响。像这样的研究将使强大的基因分型方法被用于识别那些患黑色素瘤和其他皮肤癌风险最高的个体。

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.