Bartell S M, Ponce R A, Takaro T K, Zerbe R O, Omenn G S, Faustman E M
Department of Environmental Health, University of Washington, Seattle 98105-6099, USA.
Risk Anal. 2000 Feb;20(1):87-99. doi: 10.1111/0272-4332.00009.
Genetic differences (polymorphisms) among members of a population are thought to influence susceptibility to various environmental exposures. In practice, however, this information is rarely incorporated into quantitative risk assessment and risk management. We describe an analytic framework for predicting the risk reduction and value-of-information (VOI) resulting from specific risk management applications of genetic biomarkers, and we apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leukocyte Antigen gene variant, HLA-DP beta 1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (approximately 94%) but low specificity (approximately 70%) with respect to CBD among individuals occupationally exposed to respirable beryllium. The expected postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothetical cohort with 1% baseline CBD prevalence. VOI analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed CBD intervention programs based on the genetic susceptibility test. For the example cohort, the expected net VOI per beryllium worker for genetically based testing and intervention is $13,000, $1,800, and $5,100, respectively, based on a health valuation of $1.45 million per CBD case avoided. VOI results for alternative CBD evaluations are also presented. Despite large parameter uncertainty, probabilistic analysis predicts generally positive utility for each of the three evaluated programs when avoidance of a CBD case is valued at $1 million or higher. Although the utility of a proposed risk management program may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consider serious social, legal, and ethical factors.
人群成员之间的基因差异（多态性）被认为会影响对各种环境暴露的易感性。然而，在实际中，这些信息很少被纳入定量风险评估和风险管理。我们描述了一个分析框架，用于预测基因生物标志物的特定风险管理应用所带来的风险降低和信息价值（VOI），并将该框架应用于职业性慢性铍病（CBD）的例子，这是一种免疫介导的肺部肉芽肿性疾病。一种已描述的人类白细胞抗原基因变体，即HLA - DPβ1*0201，在第69位含有谷氨酸替代赖氨酸的替换，对于职业性接触可吸入铍的个体而言，其对CBD的敏感性似乎较高（约94%），但特异性较低（约70%）。在一个基线CBD患病率为1%的假设队列中，将该基因变体用于（1）作为必需的工作安置筛查、（2）作为每半年一次的医学筛查以替代每年的淋巴细胞增殖测试、或（3）作为自愿的工作安置筛查时，干预后的预期CBD患病率分别为0.08%、0.8%和0.6%。VOI分析用于检查预期基于基因易感性测试的拟议CBD干预计划所带来的总社会成本降低，总社会成本计算为疾病减少的净值和财务支出。对于该示例队列，基于每避免一例CBD病例的健康估值为145万美元，基于基因检测和干预，每名铍工人的预期净VOI分别为13,000美元、1,800美元和5,100美元。还给出了替代性CBD评估的VOI结果。尽管存在较大参数不确定性，但当避免一例CBD病例的价值为100万美元或更高时，概率分析预测这三个评估项目中的每一个通常都具有正效用。虽然拟议的风险管理计划的效用可能仅根据风险降低和财务成本进行评估，但关于基因检测和计划实施的决策还必须考虑严重的社会、法律和伦理因素。
