Personalized Genomic Testing for Melanoma: Maximizing Personal Utility and Reach

描述（由申请人提供）：目前很少有翻译基因组研究存在，以指导在不同的，一般人群亚群中个性化基因组学的可用性，理解和适当吸收，这些亚群将在未来几年从中受益。由国家人类基因组研究所（NHGRI）领导的多重研究开发了一个互联网提供常见疾病的基因组测试和风险反馈，包括黑色素瘤风险的黑素皮质素受体基因（MC1R），这是高度可理解的，准确的解释，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，并且在西班牙裔人群中不成比例地增加。大约50%的人群中存在MC1R的高风险变异，与阳光照射相互作用，并使普通人群（甚至是皮肤较黑的人群）患黑色素瘤的风险增加2-3倍。因此，关于MC1R风险状况的反馈是提高普通人群风险意识和保护行为的潜在手段。我们提出了一项随机对照试验，通过MC1R检测检测黑色素瘤（PGT-M）个性化基因组检测的风险和益处(N=885，随机6:1 PGT-M与等候名单对照，在结果评估后提供测试，在西班牙裔和非西班牙裔种族之间平衡，PGT-M组N= 750；n=135（对照组）比较了新墨西哥州阿尔伯克基的个人效用和影响范围，那里全年都有阳光照射。目的：我将从短期（三个月）防晒、皮肤筛查（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）方面研究PGT-M的个人效用。我们假设，与拒绝测试的人相比，接受测试的人的行为和假定的中介会更高。Aim 1a将检查在接受平均风险PGT-M结果的人群中进行测试的潜在意外后果，并检查三个月后防晒的预测结果。这些发现将用于为接受平均风险反馈的群体提供信息。Aim II将比较西班牙裔和非西班牙裔的PGT-M的到达率，考虑到PGT-M检测和注册决定的利弊。我们假设西班牙裔人的覆盖率会降低，但健康素养水平、对卫生系统的不信任以及社会文化因素(癌症宿命论、

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