Marsh Gary M, Youk Ada O, Buchanich Jeanine M, Erdal Serap, Esmen Nurtan A
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Regul Toxicol Pharmacol. 2007 Aug;48(3):308-19. doi: 10.1016/j.yrtph.2007.04.006. Epub 2007 Apr 30.
To investigate further the possibility that the large nasopharyngeal cancer (NPC) mortality excess among a cohort of formaldehyde-exposed workers may be related to occupational factors external to the study plant.
Subjects were 7345 workers employed at a plastics-producing plant (1941-1984) in Wallingford, Connecticut evaluated independently as part of a National Cancer Institute cohort study. Vital status for 98% of the cohort and cause of death for 95% of 2872 deaths were determined through 2003. Reconstructed worker exposures to formaldehyde were used to compute unlagged and lagged exposure measures. We computed standardized mortality ratios (SMRs) based on US and local county rates. In a nested case-control study we evaluated mortality risks from NPC and from all other pharyngeal cancers combined (AOPC) in relation to formaldehyde exposure while accounting for potential confounding or effect modification by smoking or external (non-Wallingford) employment. Job applications, Connecticut commercial city directories and a previous survey were used to assign subjects to three external job groups.
We observed no new deaths from NPC and one additional AOPC death (pharynx unspecified) yielding, respectively, SMRs of 4.43 (7 deaths, 95% CI=1.78-9.13) and 1.71 (16 deaths, 95% CI=1.01-2.72). Five of seven NPC cases worked in silver smithing (including brass plating and other jobs related to silver or brass) or other metal work (including steel working and welding), and this type of work was relatively rare in the remaining study population (OR=14.41, 95% CI=1.08-82.1). For AOPC, we found a moderate increase in risk for other metal work (OR=1.40, 95% CI=.31-5.1). Interaction models suggested that NPC and AOPC risks were not elevated in subjects exposed only to formaldehyde.
The results of our nested case-control study suggest that the large nasopharyngeal cancer mortality excess in the Wallingford cohort may not be due to formaldehyde exposure, but rather reflects the influence of external employment in the ferrous and non-ferrous metal industries of the local area that entailed possible exposures to several suspected risk factors for upper respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts and heat). Our findings may also help to explain why the associations with formaldehyde and nasopharyngeal cancer reported in the 1994 update of the 10-plant NCI formaldehyde cohort study were unique to the Wallingford plant (Plant 1 in NCI study). Further updates of the NCI formaldehyde cohort study should include co-exposure data on silver smithing and other metal work for all study plants to help explain the unique findings for nasopharyngeal cancer in Plant 1 compared with the other nine plants.
进一步调查一组甲醛暴露工人中鼻咽癌(NPC)死亡率过高可能与研究工厂外部的职业因素有关的可能性。
研究对象为7345名受雇于康涅狄格州沃灵福德一家塑料生产厂(1941 - 1984年)的工人,作为美国国立癌症研究所队列研究的一部分进行独立评估。截至2003年,确定了该队列中98%人员的生命状态以及2872例死亡中95%人员的死亡原因。利用重建的工人甲醛暴露情况来计算未滞后和滞后的暴露指标。我们根据美国和当地县的死亡率计算标准化死亡比(SMR)。在一项巢式病例对照研究中,我们评估了与甲醛暴露相关的鼻咽癌以及所有其他合并的咽癌(AOPC)的死亡风险,同时考虑了吸烟或外部(非沃灵福德)就业可能造成的混杂或效应修正。通过求职申请、康涅狄格州商业城市名录以及之前的一项调查,将研究对象分为三个外部工作类别。
我们未观察到新的鼻咽癌死亡病例,另外有1例AOPC死亡(咽部位未明确),得出的SMR分别为4.43(7例死亡,95%可信区间=1.78 - 9.13)和1.71(16例死亡,95%可信区间=1.01 - 2.72)。7例鼻咽癌病例中有5例从事银器制作(包括镀黄铜及其他与银或黄铜相关的工作)或其他金属加工(包括钢铁加工和焊接),而这类工作在其余研究人群中相对较少(比值比=14.41,95%可信区间=1.08 - 82.1)。对于AOPC,我们发现其他金属加工的风险有适度增加(比值比=1.40,95%可信区间=0.31 - 5.1)。交互作用模型表明,仅暴露于甲醛的研究对象中,鼻咽癌和AOPC的风险并未升高。
我们巢式病例对照研究的结果表明,沃灵福德队列中鼻咽癌死亡率过高可能并非由于甲醛暴露,而是反映了当地黑色和有色金属行业外部就业的影响,这可能导致接触几种上呼吸道癌症的疑似风险因素(如硫酸雾、无机酸、金属粉尘和热)。我们的研究结果也可能有助于解释为什么在10家工厂的美国国立癌症研究所甲醛队列研究1994年更新版中报告的甲醛与鼻咽癌之间的关联仅在沃灵福德工厂(美国国立癌症研究所研究中的工厂1)中出现。美国国立癌症研究所甲醛队列研究的进一步更新应纳入所有研究工厂银器制作和其他金属加工的共暴露数据,以帮助解释工厂1与其他9家工厂相比鼻咽癌的独特研究结果。