Multiple Myeloma Consortium Study of Occupational Exposures and Family History

描述(由申请人提供)：在某些职业和一般环境中，接触溶剂的情况很普遍。对于可疑的和已知的致癌物，包括三氯乙烯(TCE)和苯，特别是对于那些描述较少或这种联系存在争议的癌症部位，迫切需要量化致癌风险的数据。有研究表明，这些溶剂和其他溶剂可能会增加多发性骨髓瘤(MM)的风险；然而，由于这种疾病的罕见，针对MM的个别、地区性流行病学研究一直受到严重限制，阻碍了对这些联系的信心描述。需要更多的数字来研究职业性溶剂暴露，特别是在描述不同暴露强度水平或持续时间增加的风险时。通过结合现有多发性骨髓瘤流行病学数据资源进行协作重新分析的有效方法，我们将汇集参加国际多发性骨髓瘤联合会(IMMC)的13项病例对照研究的数据，以进行迄今最有力的与职业溶剂暴露相关的风险研究。参与IMMC的已完成研究包括3600多个病例和12,000个对照，以及关于职业的问卷数据(例如，有或没有其他问题的职称/行业 任务和暴露)，基于这些数据，我们将评估对五种特别感兴趣的特定溶剂的暴露：三氯乙烯(TCE)、全氯乙烯(PCE)、苯、甲苯和二甲苯。淋巴造血癌家族史对于协调IMMC研究也很重要，因为它可能是多发性骨髓瘤的危险因素，因此也是一个关键因素，可以考虑作为职业或其他暴露的潜在混杂因素或效应修饰物(作为患多发性骨髓瘤遗传易感性的指标)。例如，我们将探索职业溶剂暴露与这些癌症家族史在多发性骨髓瘤发生中的相互作用，这种相互作用已被建议用于非霍奇金淋巴瘤，并可能表明在淋巴瘤病因学中遗传变异和溶剂暴露之间的相互作用。IMMC是目前解决我们研究目标的最佳(也可能是唯一的)环境，这不仅是因为研究的规模，而且因为参与的病例对照研究收集了职业和家族史的详细程度，这在典型的队列研究中是不匹配的。我们在编码和协调所有参与研究的变量方面的努力将为未来联盟研究其他职业暴露、与家族性与非家族性MM相关的遗传变异以及基因与环境的相互作用提供宝贵的资源。

DESCRIPTION (provided by applicant): Exposure to solvents is widespread, both in certain occupations and in the general environment. There is a strong need for data quantifying cancer risks for suspected and known carcinogens, including trichcloroethylene (TCE) and benzene, particularly for cancer sites that are less well-described or for which the association is controversial. There are studies suggesting that these and other solvents may increase the risk of multiple myeloma (MM); however, individual, regionally-based epidemiologic studies of MM have been severely limited by the disease's rarity, hindering the ability to describe these associations with confidence. Much larger numbers are needed to study occupational solvent exposures, particularly to characterize risks across varying exposure intensity levels or with increasing duration. With an efficient approach of combining existing MM epidemiologic data resources for collaborative reanalyses, we will pool data from 13 case-control studies participating in the International Multiple Myeloma Consortium (IMMC) to conduct the most powerful study to date of risks associated with occupational solvent exposures. Completed studies participating in the IMMC include over 3600 cases and 12,000 controls with questionnaire data on occupation (e.g., job title/industry with- or without additional questions on tasks and exposures), and based on these data we will assess exposure to five specific solvents of particular interest: trichloroethylene (TCE), perchloroethylene (PCE), benzene, toluene, and xylene. Family history of lymphohematopoietic cancers is also important to harmonize across IMMC studies as it is a likely risk factor for MM and therefore a critical factor to consider as a potential confounder or effect modifier (as an indicator of inherited susceptibiliy to develop MM) of occupational or other exposures. For example, we will explore interactions between occupational solvent exposures and family history of these cancers in development of MM, an interaction that has been suggested for non-Hodgkin lymphoma, and which may indicate an interaction between genetic variants and solvent exposure in lymphoma etiology. The IMMC is the best (and perhaps the only) current setting to address our study aims, not only because of the study size, but because the participating case-control studies collected occupational and family histories with a level of detail that isn't matched in typical cohort studis. Our effort in coding and harmonizing variables across participating studies will develop a valuable resource for future consortium studies of other occupational exposures, genetic variants associated with familial- versus non- familial MM, and gene-environment interactions.