DIVERGENT CAUSAL PATHWAYS TO MELANOMA: A COMBINED ANALYSIS OF 12 CASE-CONTROL STU

描述（由申请人提供）：黑色素瘤是由皮肤色素细胞引起的常见癌症。在美国，每年有超过62，000人被诊断患有侵袭性黑色素瘤，每年导致近8，000人死亡。阳光是导致黑色素瘤的主要因素，尽管越来越多的证据表明，阳光在导致黑色素瘤中的作用对所有人来说并不相同。我们最近提出了黑色素瘤发展的“分歧途径”假说。在这个模型下，我们认为那些容易发展痣（痣）的人患黑色素瘤的风险高于平均水平。我们假设这些人在适度的阳光照射后会发展成黑色素瘤，并且会在具有大量色素细胞的身体部位（如背部）发生。相比之下，其他不太容易发生痣的人需要暴露于大量累积剂量的阳光下才能发生黑色素瘤，这些黑色素瘤往往会出现在习惯性暴露于阳光的身体部位，如头部和颈部。支持这一假设的流行病学和分子证据已经发表，基于对小数据集的分析。这个新项目旨在通过对从12项病例对照研究中收集的原始研究数据进行系统的重新分析来测试黑色素瘤发展的发散途径假设，这些研究包括2，954名黑色素瘤患者和3，685名健康对照的个人数据记录。主要目的是将患有在不同身体部位（躯干、头颈部、上肢、下肢）产生的黑素瘤的患者与无黑素瘤的对照进行比较，以确定各组之间痣和日光暴露的分布是否不同。完成后，这项研究将提供有关黑色素瘤病因的新信息。这些知识对于控制和预防这种癌症至关重要。黑色素瘤是由阳光引起的常见皮肤癌。该项目旨在发现不同身体部位的黑色素瘤是否是通过不同的因果因素组合产生的。最终，这项研究的结果可能有助于更好的预防策略，以减少死于黑色素瘤的人数（目前美国每年有8000人）。

DESCRIPTION (provided by applicant): Melanomas are common cancers arising from the pigment cells of the skin. Each year, more than 62,000 people are diagnosed with invasive melanoma in the United States, resulting in almost 8,000 deaths annually. Sunlight is the principal factor that causes melanoma, although there is increasing evidence that the role of sunlight in causing melanoma is not the same for all people. We have recently proposed a "divergent pathway" hypothesis for the development of melanoma. Under this model, we posit that people who are prone to develop nevi (moles) are at higher-than-average risk for melanoma. We hypothesize that such people will develop melanoma after modest amounts of sun exposure, and will do so on body sites with large populations of pigment cells such as the back. In contrast, other people who are less prone to developing nevi require exposure to large cumulative doses of sunlight to develop melanoma, and these melanomas will tend to arise on habitually sun-exposed body sites such as the head and neck. Epidemiologic and molecular evidence in support of this hypothesis has been published based on analyses of small datasets. This new project aims to test the divergent pathway hypothesis for the development of melanoma by undertaking a systematic re-analysis of the original study data collected from 12 case-control studies comprising individual data records for 2,954 people with melanoma and 3,685 healthy controls. The primary objective is to compare patients with melanomas arising at different body sites (trunk, head & neck, upper limb, lower limb) with melanoma- free controls to determine whether the distribution of nevi and sun exposure differs among the groups. When complete, this study will provide new information about the causes of melanoma. Such knowledge is crucial to controlling and preventing this cancer. Melanomas are common cancers of the skin caused by sunlight. This project aims to find whether melanomas at different body sites arise through different combinations of causal factors. Ultimately, the results of this research may contribute to better preventive strategies to reduce the number of people who die from melanoma (currently 8000 people each year in the United States).