Personalized Genomic Testing for Melanoma: Maximizing Personal Utility and Reach

描述(由申请人提供)：目前几乎没有翻译基因组研究来指导个性化基因组学在未来几年将从中受益的不同的、一般的人群亚群中的可用性、理解力和适当的吸收。由国家人类基因组研究所(NHGRI)领导的Multiplex研究开发了一种针对常见疾病(包括黑色素瘤风险的黑素皮质素受体基因(MC1R))的基因组测试和风险反馈的互联网服务，具有高度可理解、准确解释的特点，并且不会增加初级保健人群的痛苦。黑色素瘤皮肤癌是可预防、可治愈的，在普通人群中很常见，在西班牙裔中不成比例地增加。MC1R的高风险变异存在于大约50%的人群中，与阳光照射相互作用，在普通人群--甚至是较黑的皮肤人群--中增加2-3倍的黑色素瘤风险，因此关于MC1R风险状态的反馈是提高普通人群的风险意识和保护行为的潜在工具。我们提出了一项随机对照试验，通过MC1R测试(N=885，随机6：1 PGT-M与等待名单对照提供的结果评估后提供的测试，在PGT-M组中平衡西班牙裔和非西班牙裔，n=750在PGT-M组中；n=135在控制组中)通过MC1R测试来检验互联网呈现的黑色素瘤个性化基因组测试的风险和好处)比较在新墨西哥州阿尔伯克基的普通人群队列中的个人效用和覆盖范围，那里全年都有阳光暴晒。目的我将从短期(3个月)防晒、皮肤屏蔽(即行为)、沟通、黑色素瘤威胁和控制信念(即行为改变的假定中介)方面考察PGT-M的个人效用。我们假设，与拒绝测试的人相比，测试的人的行为和假定的中介因素会更高。Aim 1a将在那些接受平均风险PGT-M检测结果的患者中检查潜在的意外后果，并检查作为结果的三个月后防晒的预测因素。这些发现将被用来为收到平均风险反馈的群体制定信息。AIM II将从测试和注册PGT-M决定的利弊考虑，比较西班牙裔和非西班牙裔的PGT-M的达标率。我们假设拉美裔美国人将表现出覆盖范围的减少，但健康素养、卫生系统不信任和社会文化因素(癌症宿命论， 家庭健康取向、皮肤癌误解)将解释拉美裔和非拉美裔之间REACH的差异，并为未来针对拉美裔的PGT-M修改提供指导。AIM III将检查接受测试的人的PGT-M反馈理解、回忆、满意度和癌症相关痛苦，以及这些结果是否因种族(西班牙裔与非西班牙裔)或社会文化或人口因素而不同。目前的研究将是第一次使用建立的MULPLEX邀请进行皮肤癌遗传风险测试来检查行为结果，也是第一次使用MULPLEX参与拉美裔人口-这两项研究都没有在最初的MULPLEX研究中涉及。这项研究将对黑色素瘤背景下的个性化基因组学产生重要影响，并将广泛应用于其他疾病的个性化基因组反馈的传递模式。PHS 398/2590(06/09版)页面续格式页面

DESCRIPTION (provided by applicant): Currently little translational genomic research exists to guide the availability, comprehension, and appropriate uptake of personalized genomics in diverse, general population subgroups that stand to benefit from it in the coming years. The Multiplex Study led by the National Human Genome Research Institute (NHGRI) developed an Internet offer of genomic testing and risk feedback for common diseases, including the melanocortin receptor gene (MC1R) for melanoma risk, that was highly comprehensible, accurately interpreted, and did not increase distress in a primary care population. Melanoma skin cancers are preventable, curable, common in the general population, and disproportionately increasing in Hispanics. Higher risk variants in MC1R are present in about 50% of the population, interact with sun exposure, and confer 2-3 fold melanoma risk in the general population - even darker skin populations - thus feedback regarding MC1R risk status is a potential vehicle to raise risk awareness and protective behavior in the general population. We propose a randomized controlled trial examining Internet presentation of the risks and benefits of personalized genomic testing for melanoma (PGT-M) via MC1R testing (N=885, randomized 6:1 PGT-M versus waiting list control offered testing after outcome assessments, balanced across Hispanic versus Non-Hispanic ethnicity, n=750 in PGT-M arm; n=135 in control arm) comparing personal utility and reach in a general population cohort in Albuquerque New Mexico, where there is year-round sun exposure. Aim I will examine the personal utility of PGT-M in terms of short-term (three month) sun protection, skin screening (i.e., behaviors), communication, melanoma threat and control beliefs (i.e., putative mediators of behavior change). We hypothesize that behaviors and putative mediators will be higher in those who test compared to those who decline testing. Aim 1a will examine potential unintended consequences of testing among those who receive average risk PGT-M findings, examining predictors of sun protection at three months as the outcome. These findings will be used to develop messages for groups that receive average risk feedback. Aim II will compare rates of reach of PGT-M in Hispanic versus Non-Hispanics in terms of consideration of the pros and cons of testing and registration of PGT-M decision. We hypothesize that Hispanics will show reduced reach, but that levels of health literacy, health system distrust, and sociocultural factors (cancer fatalism, family health orientation, skin cancer misconceptions) will explain differences in reach between Hispanics and Non- Hispanics, and provide guidance for future PGT-M modifications for Hispanics. Aim III will examine PGT-M feedback comprehension, recall, satisfaction, and cancer-related distress in those who undergo testing, and whether these outcomes differ by ethnicity (Hispanic versus Non-Hispanic) or sociocultural or demographic factors. The current study will be the first to use the established Multiplex invitation for skin cancer genetic risk testing to examine behavioral outcomes, and the first to use Multiplex to engage a Hispanic population - neither was addressed in the original Multiplex Study. The study will have important implications for personalized genomics in the melanoma context, and will be broadly applicable as a model for delivery of personalized genomic feedback for other conditions, as well. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page