Cancer Risk and Environmental Exposures

研究环境中癌症的危险因素，以确定特定的化学物质和污染物类别，调查其作用机制，并估计环境因素对普通人群癌症的贡献。暴露包括饮用水污染物，特别是消毒副产物、硝酸盐和砷；家中空气中的氡；氯代烃的居住水平和人体负荷；以及工业排放。爱荷华州的病例对照研究表明，长期饮用饮用水中的消毒副产物后，男女患直肠癌和膀胱癌和脑癌的风险都很高。正在对这些数据进行分析，并改进和更新对消毒副产物暴露的评估。在西班牙，长期暴露于消毒副产物后膀胱癌发病率升高，基因型为GSTT1（+）或GSTZ1 （SNP rs1046428）的人群风险增加。还观察到膀胱癌的风险与通过非摄入途径（例如吸入或皮肤吸收）暴露于dbp有关。我们目前正在新英格兰的一项病例对照研究中评估这一假设。爱荷华州公共供水中的硝酸盐水平与膀胱癌和胰腺癌的风险无关。我们观察到，在亚硝化能力增强的亚组中，结肠癌和肾癌的风险增加，这分别是由于他们摄入了更多的饮用水硝酸盐，摄入了更少和更多的维生素C和红肉。在爱荷华州一项针对老年妇女的队列研究中，在公共供水中摄入较高浓度的硝酸盐以及较高的饮食摄入量与患甲状腺癌的风险增加有关。饮食中硝酸盐的摄入与甲状腺功能减退有关。巢式病例对照研究正在进行中，以评估多卤芳烃（PHAH）与甲状腺癌风险的关系。膀胱癌的风险增加后，暴露于砷水平的饮用水供应的最大污染物的限制数倍。在新英格兰北部进行的一项病例对照研究正在评估在美国更常见的较低水平的膀胱风险。我们为95%的参与者分配了居住人年和86%的职业人年的住宅供水砷浓度。在加利福尼亚的一项病例对照研究中，地毯灰尘被用作暴露指标，以检查儿童白血病风险与多氯联苯（PCB）和有机氯农药的住宅暴露有关。随着多氯联苯同系物118、138和153浓度的增加，急性淋巴细胞白血病（ALL）风险呈显著阳性趋势。我们之前在一项多中心研究中发现血清和家居粉尘样本中的多氯联苯与成人非霍奇金淋巴瘤（NHL）风险之间存在关联。我们评估了三种暴露风险升高的免疫基因变异是否改变了这种关系：PCB180（血浆，粉尘测量），血浆毒性当量商（TEQ）和-氯丹（粉尘测量，自我报告的白蚁剂使用）。所有三种暴露与NHL风险之间的关联仅限于IFNG (C-1615T) TT和IL4 (5'-UTR, Ex1-168C>T) CC的相同基因型，血浆和粉尘中PCB180与NHL风险之间的关联仅限于IL16 (3'-UTR, Ex22+871A>G) AA, IL8 (T- 251a) TT和IL10 (A-1082G) AG/GG的相同基因型。目前在家庭和农业中使用的许多农药不会在体内持久存在，因此生物标志物不是长期暴露的有用衡量标准。我们比较了两种方法收集的粉尘样本中的农药和其他化学物质的浓度，一种是专用真空（HVS3），另一种是参与者自己的真空袋，发现农药、多氯联苯、多环芳烃（PAH）和金属之间存在很强的相关性。在ALL的病例对照研究中，我们使用GIS来改进指标，以评估住宅附近的农药使用情况，使用有关住宅附近作物当前和历史位置的信息。与较短的时间间隔相比，前两年在房屋周围使用的特定农业农药与室内粉尘浓度的关系最强。将评估基于gis的农药指标与ALL风险的关系。使用地理信息系统，在NHL病例对照研究中评估了向环境保护局有毒物质释放清单报告的特定工业的住宅邻近程度。观察到木材和木制品设施与NHL风险增加有关，特别是弥漫性大b细胞淋巴瘤（居住在2英里内：OR=1.7, 95% CI: 1.0-3.0）。我们观察到居住在化学工业（OR=1.5, 95% CI: 1.1-2.0）和石油工业（OR=1.9, 95% CI: 1.0-3.6）附近的10年以上的ORs升高。目前正在对与二恶英排放源有关的NHL风险进行分析。一项针对密苏里州妇女的肺癌和住宅氡的病例对照研究使用了一种新型氡探测器，该探测器综合了过去30年的暴露情况，观察到肺癌风险显著增加。来自密苏里研究和爱荷华研究的病理学和流行病学数据将被合并进行汇总分析。一项对1917年至1951年出生的中国宣威农民的回顾性队列研究表明，烟煤和无烟煤的年吨位和终生使用时间与肺炎死亡率呈正相关，炉子的改进与男性(风险比（HR)=0.62, 95%可信区间(CI)=0.46-0.82）和女性（HR=0.41, 95% CI=0.29-0.57）的肺炎死亡率和肺癌死亡率降低50%相关。中国宣威的一项病例对照研究根据煤炭类型评估了肺癌的风险，发现该地区使用不同类型煤炭的肺癌风险存在显著差异，比值比从1.1到27.0不等。

Risk factors for cancer from the ambient environment are studied to identify specific chemicals and classes of contaminants, to investigate mechanisms of action, and to estimate the contribution of environmental factors to cancer in the general population. Exposures include drinking water contaminants, especially disinfection byproducts, nitrate, and arsenic; airborne radon in homes; residential levels and body burdens of chlorinated hydrocarbons; and emissions from industrial sources. Case-control studies in Iowa showed excess risks for rectal cancer in both sexes and bladder and brain cancers among men after long-term consumption of disinfection byproducts in drinking water. Analysis of these data with an improved and updated assessment of exposure to disinfection byproducts is ongoing. Bladder cancer in Spain was elevated after long-term exposure to disinfection byproducts, with enhanced risk among persons with genotypes GSTT1 (+) or GSTZ1 (with SNP rs1046428). It was also observed that risk of bladder cancer was associated with exposure to DBPs through routes other than ingestion (e.g., inhalation or dermal absorption). We are currently evaluating this hypothesis in a case-control study in New England. Nitrate levels in public water supplies in Iowa were not associated with risk of bladder and pancreas cancer. We observed increased risks of colon and kidney cancer among subgroups with increased nitrosation ability due to their higher intake of drinking water nitrate and lower and higher intakes of vitamin C and red meat, respectively. Ingestion of higher nitrate concentrations in public water supplies as well as higher dietary intake was associated with increased risk of thyroid cancer in a cohort study of older women in Iowa. Dietary nitrate intake was associated with hypothyroidism. Nested case-control studies are ongoing to evaluate polyhalogenated aromatic hydrocarbons (PHAH) in relation to risk of thyroid cancer. Bladder cancer risk is increased after exposure to arsenic in drinking water supplies at levels several times the maximum contaminant limit. A case-control study in northern New England is evaluating bladder risk at lower levels that are more common in the United States. We have assigned a residential water supply arsenic concentration for 95% of participants residential person-years and 86% of occupational person-years. Carpet dust was used as an exposure indicator to examine the risk of childhood leukemia in relation to residential exposure to polychlorinated biphenyls (PCB) and organochlorine pesticides in a case control study in California. Significant positive trends in acute lymphocytic leukemia (ALL) risk were apparent with increasing concentrations of PCB congeners 118, 138, and 153. We earlier found an association between PCBs in serum and household dust samples and risk of adult non-Hodgkin's lymphoma (NHL) in a multi-center study. We evaluated whether this relation is modified by immune gene variation for 3 exposures with elevated risk: PCB180 (plasma, dust measurements), the toxic equivalency quotient (TEQ) in plasma, and alpha-chlordane (dust measurements, self-reported termiticide use). Associations between all 3 exposures and NHL risk were limited to the same genotypes for IFNG (C-1615T) TT and IL4 (5'-UTR, Ex1-168C>T) CC. Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3'-UTR, Ex22+871A>G) AA, IL8 (T-251A) TT, and IL10 (A-1082G) AG/GG. Many pesticides in current use around the home and in agriculture are not persistent in the body so biomarkers are not useful measures of long-term exposure. We compared concentrations of pesticides and other chemicals in dust samples collected by two methods, a specialized vacuum (the HVS3) and participant's own vacuum bag and found strong correlations for pesticides, PCBs, polycyclic aromatic hydrocarbons (PAH), and metals. Using a GIS in the case-control study of ALL, we refined metrics to evaluate agricultural pesticide use near residences, using information about the current and historical location of crops near homes. For specific agricultural pesticides use around homes in the prior two years showed the strongest relationship with concentrations in house dust compared with shorter time intervals. GIS-based pesticide metrics will be evaluated in relation to risk of ALL. Using a GIS, residential proximity to specific industries reporting to the Environmental Protection Agency's Toxic Release Inventory was evaluated in the NHL case-control study. Increased risk of NHL was observed in relation to lumber and wood products facilities especially for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7, 95% CI: 1.0-3.0). We observed elevated ORs for the 10+ years duration living near the chemical (OR=1.5, 95% CI: 1.1-2.0) and petroleum (OR=1.9, 95% CI: 1.0-3.6) industries. Analysis of NHL risk in relation to sources of dioxin emissions is ongoing. A case-control study of lung cancer and residential radon among Missouri women used a novel radon detector that integrated exposure over the past 30 years and observed significant excess lung cancer risk. Pathology and epidemiology data from the Missouri study and an Iowa study will be combined for a pooled analysis. A retrospective cohort study of farmers born 1917 through 1951 and living in Xuanwei, China demonstrated that annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality and that stove improvement was associated with a 50% reduction in pneumonia deaths and with decreased risk of lung cancer mortality in men (hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.46-0.82) and women (HR=0.41, 95% CI=0.29-0.57). A case-control study in Xuanwei, China evaluated the risk of lung cancer by coal type and found a striking variation in risk of lung cancer from use of different types of coal in this region, with odds ratios varying from 1.1 up to 27.0.