Molecular Epidemiology of Melanoma

色素沉着表型（例如，头发颜色）和对日光暴露的反应（例如，雀斑、晒伤）与黑色素瘤风险有关。 然而，也有强有力的证据表明，基因型，内源性生理和外源性暴露的组合影响黑色素瘤的风险。 特别是，参与色素沉着途径和对环境暴露的反应的遗传基因型（例如，紫外线阳光照射）可能会改变一个人的风险发展黑色素瘤。 这些基因包括参与黑素生成的基因，如黑皮质素1受体（MC1R）、酪氨酸酶（TYR）、酪氨酸相关蛋白（TRP1、TRP2）和P基因。 除了色素沉着特征和紫外线阳光照射外，有关这些基因相互作用的知识可能会提高识别黑色素瘤风险增加的个体的能力。 这些知识可以反过来用于针对个体的原发性或继发性黑色素瘤预防策略。我们提出了一个病例对照研究，将直接解决黑色素瘤的复杂，多因素的病因，涉及色素沉着途径和其他危险因素的基因型的相互作用。 本研究将探讨一些具体的假设。 首先，我们将描述候选易感基因型。 其次，我们将评估基因型是否与色素沉着特征相关（特别是与黑色素瘤风险相关的基因型），以及基因型是否与肿瘤特征相关，包括诊断时的分期、分级和年龄。最后，我们将评估这些基因型是否参与黑色素瘤的病因，以及这些基因型是否相互作用和其他黑色素瘤的危险因素。为了解决这些假设，我们将利用宾夕法尼亚大学色素病变组的广泛资源进行一项研究。 样本将包括1000例黑色素瘤病例和1000例对照。 将通过问卷调查获得风险因素信息，将使用非侵入性颊拭子方法收集DNA生物样本，并将使用系统方法收集诊断病理学信息。将进行分析，以评估候选基因型和其他风险因素在黑色素瘤病因学中的作用，包括基因型与环境的相互作用。

Pigmentation phenotypes (e.g., hair color) and response to sun exposure (e.g., freckling, sunburns) have been associated with melanoma risk. However, there is also strong evidence that a combination of genotypes, endogenous physiology, and exogenous exposures influence melanoma risk. In particular, inherited genotypes involved in pigmentation pathways and response to environmental exposures (e.g., UV sun exposure) may modify an individual's risk of developing melanoma. These genes include those involved in melanogenesis, such as the melanocortin 1 receptor (MC1R), tyrosinase (TYR), the tyrosine-related proteins (TRP1, TRP2), and the P gene. Knowledge about interactions of these genes in addition to pigmentation characteristics and UV sun exposure may improve the ability to identify individuals at increased melanoma risk. This knowledge may in turn be used to target individuals for primary or secondary melanoma prevention strategies. We propose a case-control study that will directly address the complex, multifactorial etiology of melanoma that involves the interaction of genotypes involved in pigmentation pathways and other risk factors. This study will address a number of specific hypotheses. First, we will characterize candidate susceptibility genotypes. Second, we will evaluate whether genotypes are associated with pigmentation characteristics (in particular those that are associated with melanoma risk), and whether genotypes are associated with tumor characteristics, including stage, grade, and age at diagnosis., Finally, we will evaluate whether these genotypes are involved in melanoma etiology, and whether these genotypes interact with one another and other melanoma risk factors. In order to address these hypotheses, we will undertake a study using the extensive resources of the Pigmented Lesion Group at the University of Pennsylvania. The sample will consist of 1000 melanoma cases and 1000 controls. Risk factor information will be obtained by questionnaire, a DNA biosample will be collected using a non-invasive cheek swab method, and diagnostic pathology information will be collected using a systematic approach. Analyses will be undertaken to evaluate the role of candidate genotypes and other risk factors in melanoma etiology, including genotype by environment interactions.