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。爱荷华州妇女健康研究（一项对爱荷华州老年妇女的队列研究）表明，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。在一项对宾夕法尼亚州旧秩序阿米什人的队列研究中，私人水井中较高的硝酸盐水平与妇女亚临床甲状腺功能减退的患病率增加有关。巢式病例对照研究正在进行中，以评估多卤芳烃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。地毯灰尘中多溴二苯醚（PBDEs）的总含量与ALL风险无关；然而，对于特定的八溴二苯醚同系物，包括BDE-196、BDE-203、BDE-206和BDE-207，风险增加了约2倍。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, Ex1-168CT) 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+871AG) 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。在爱荷华州妇女健康研究队列中，农场居住与急性髓性白血病风险增加相关。农作物的密度并不能解释这种关联；然而，与不种植行栽作物的妇女相比，750米范围内的行栽作物密度与慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的发病率升高相关（RR增加值=1.4、1.5和1.6）。在NHL病例对照研究中，对向环境保护署有毒物质释放清单报告的特定工业附近的住宅进行了评估。观察到与木材/木制品相关的风险增加，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）。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。靠近水泥窑和危险废物焚化炉排放的二恶英/呋喃与来自家庭的粉尘样本中的高浓度有关。住宅靠近某些二恶英/呋喃源，NHL风险也会增加。先前的分析表明，家庭中多氯联苯含量越高，患非霍奇金淋巴瘤的风险就越大。家庭中多氯联苯水平的决定因素包括人口密度、住宅附近的已开发土地和2公里内工业设施的数量，这表明室外多氯联苯来源可能是室内浓度的重要决定因素。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。中国宣威的一项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，并且在男性(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）中，炉子的改进与肺炎死亡率降低50%和肺癌死亡率降低相关。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。在一项针对上海城市女性的前瞻性队列研究中，与从不通风不良的厨房相比，通风不良的厨房与肺癌风险增加49%相关（HR: 1.49; 95% CI: 1.15-1.95）。使用煤炭与风险无关；然而，曾经使用通风不良的煤炭（HR: 1.69; 95% CI: 1.22-2.35）和20年或更长时间使用通风不良的煤炭（HR: 2.03; 95% CI: 1.35-3.05）也与肺癌风险显著相关，这突出了中国城市中一个重要的公共卫生问题，人们可能生活在厨房通风不足的家庭中。

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 the Iowa Womens Health study, a cohort study of older women in Iowa. Dietary nitrate intake was associated with hypothyroidism. Higher nitrate levels in private wells were associated with increased prevalence of subclinical hypothyroidism among women in a cohort study of Old Order Amish in Pennsylvania. Nested case-control studies are ongoing to evaluate polyhalogenated aromatic hydrocarbons 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. Summed levels of polybrominated diphenyls ethers (PBDEs) in carpet dust were not associated with ALL risk; however, risk was increased approximately 2-times for specific OctaPBDE congeners including BDE-196, BDE-203, BDE-206 and BDE-207. 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, Ex1-168CT) CC. Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3'-UTR, Ex22+871AG) 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. Farm residence was associated with an increased risk of acute myeloid leukemia in the Iowa Womens Health Study cohort. Density of agricultural crops did not explain this association; however, row crop density within 750 m of homes was associated with elevated incidence of chronic lymphocytic leukemia/small lymphocytic lymphoma (RR increasing tertiles=1.4, 1.5 and 1.6) compared with women with no row crops. 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 was observed in relation to lumber/wood products especially for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7, 95% CI: 1.0-3.0). ORs were elevated for 10+ years living near chemical (OR=1.5, 95% CI: 1.1-2.0) and petroleum (OR=1.9, 95% CI: 1.0-3.6) industries. Proximity to emissions of dioxins/furans from cement kilns and hazardous waste incinerators was associated with higher concentrations in dust samples from homes. NHL risk was also increased with residential proximity to some dioxin/furan sources. Prior analyses showed increased risk of NHL with higher levels of PCBs in homes. Determinants of PCB levels in homes included population density, developed land near homes and the number of industrial facilities within 2 km, suggesting that outdoor sources of PCBs may be significant determinants of indoor concentrations. 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. A retrospective cohort study 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. In a prospective cohort of urban women in Shanghai, poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15-1.95) compared to never having poor ventilation. Use of coal was not associated with risk; however, ever use of coal use with poor ventilation (HR: 1.69; 95% CI: 1.22-2.35) and 20 or more years of using coal with poor ventilation (HR: 2.03; 95% CI: 1.35-3.05) were also significantly associated with lung cancer risk highlighting an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation.