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学研究可以指导个性化基因组学在未来几年受益的不同一般人群亚组中的可用性，理解和适当吸收。由国家人类基因组研究所（NHGRI）领导的多重研究开发了一种互联网提供的常见疾病的基因组检测和风险反馈，包括黑色素瘤风险的黑皮质素受体基因（MC 1 R），该基因高度可理解，准确解释，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，在西班牙裔中不成比例地增加。MC 1 R中的高风险变体存在于约50%的人群中，与阳光照射相互作用，并在一般人群中赋予2-3倍的黑色素瘤风险-甚至是深色皮肤人群-因此，关于MC 1 R风险状态的反馈是提高一般人群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MC 1 R检测检查黑色素瘤（PGT-M）个性化基因组检测的风险和益处的互联网呈现（N=885，PGT-M组与等待名单对照组的随机化比例为6：1，在结局评估后提供检测，西班牙裔与非西班牙裔种族之间平衡，PGT-M组n=750;对照组n=135），比较新墨西哥州的阿尔伯克基（Albuquerque）的一般人群队列中的个人效用和可及性。目的我将研究PGT-M在短期（三个月）防晒、皮肤筛查（即，行为）、沟通、黑素瘤威胁和控制信念（即，行为改变的假定介质）。我们假设，行为和假定的调解人将在那些谁测试相比，那些谁拒绝测试。目标1a将检查那些接受平均风险PGT-M结果的人中测试的潜在意外后果，检查三个月时防晒的预测因素。这些发现将用于为收到平均风险反馈的群体制定信息。目标二将比较西班牙裔与非西班牙裔PGT-M的普及率，考虑PGT-M决定的测试和注册的利弊。我们假设西班牙裔将显示出减少的影响，但健康素养，卫生系统的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）将解释西班牙裔和非西班牙裔之间的差异，并为西班牙裔未来的PGT-M修改提供指导。目标III将检查PGT-M反馈的理解，回忆，满意度和癌症相关的痛苦在那些谁接受测试，以及这些结果是否不同的种族（西班牙裔与非西班牙裔）或社会文化或人口因素。目前的研究将是第一个使用已建立的皮肤癌遗传风险测试的多重邀请来检查行为结果的研究，也是第一个使用多重邀请来参与西班牙裔人群的研究-这两个问题都没有在最初的多重研究中得到解决。该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，并将广泛适用于作为其他条件下个性化基因组反馈的模型。PHS 398/2590（Rev.06/09）

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