Cancer Risk and Environmental Exposures

研究周围环境中的癌症风险因素，以确定特定的化学物质和污染物类别，研究作用机制，并估计环境因素对一般人群癌症的影响。暴露包括饮用水污染物，特别是消毒副产品，硝酸盐和砷;家庭空气中的氡;氯化烃的住宅水平和身体负担;以及工业源的排放。爱荷华州的病例对照研究表明，长期饮用消毒副产品后，男女患直肠癌的风险都很高，男性患膀胱癌和脑癌的风险也很高。正在对这些数据进行分析，并对消毒副产品暴露进行改进和更新评估。西班牙的膀胱癌在长期暴露于消毒副产品后升高，具有GSTT 1（+）或GSTZ 1（SNP rs 1046428）基因型的人的风险增加。还观察到膀胱癌的风险与通过摄入以外的途径（例如，吸入或皮肤吸收）。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。我们观察到亚硝化能力增加的亚组中结肠癌和肾癌的风险增加，这是由于他们分别摄入了较高的饮用水硝酸盐和较低和较高的维生素C和红肉摄入量。在爱荷华州的一项老年妇女队列研究中，公共供水中硝酸盐浓度较高的摄入以及较高的饮食摄入与甲状腺癌风险增加有关。b饮用水中的砷含量数倍于最大污染物限值，接触砷后患膀胱癌的风险增加。一项在北方新英格兰进行的病例对照研究正在评估膀胱风险在美国更常见的较低水平。我们已经分配了一个住宅供水砷浓度为95%的参与者住宅人年和86%的职业人年。 在加州的一项病例对照研究中，地毯灰尘被用作暴露指标，以检查儿童白血病与住宅暴露于多氯联苯（PCB）和有机氯农药的风险。随着多氯联苯同系物118、138和153浓度的增加，急性淋巴细胞性白血病（ALL）风险明显呈上升趋势。我们早先在一项多中心研究中发现，血清和家庭灰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。我们评估了这种关系是否被免疫基因变异改变了3个风险升高的暴露：PCB 180（血浆，粉尘测量），血浆中的毒性当量商数（TEQ），和α-氯代乙酰胺（粉尘测量，自我报告的杀白蚁剂使用）。所有3种暴露与NHL风险之间的关联仅限于IFNG（C-1615 T）TT和IL 4（5 '-UTR，Ex 1 - 168 C>T）CC的相同基因型。血浆和粉尘中PCB 180与NHL风险之间的关联仅限于IL 16（3 '-UTR，Ex 22 + 871 A>G）AA、IL 8（T-251 A）TT和IL 10（A-1082 G）AG/GG的相同基因型。目前在家庭和农业中使用的许多农药在体内并不持久，因此生物标志物并不是长期暴露的有用措施。我们比较了通过两种方法收集的灰尘样本中农药和其他化学物质的浓度，一种是专门的真空（HVS 3），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）和金属具有很强的相关性。在ALL的病例对照研究中使用GIS，我们正在改进指标，以评估住宅附近的农业农药使用，使用有关住宅附近作物的当前和历史位置的信息。使用地理信息系统，住宅接近特定行业的报告，环境保护局的有毒物质释放清单进行了评估，在NHL的病例对照研究。观察到与木材和木制品设施相关的NHL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）。我们观察到在化工（OR=1.5，95% CI：1.1-2.0）和石油（OR=1.9，95% CI：1.0-3.6）行业附近生活10年以上的OR升高。目前正在分析与二恶英排放源有关的非霍奇金淋巴瘤风险。一项关于密苏里州妇女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。正在进一步验证这种剂量测定技术。将合并来自密苏里州研究和爱荷华州研究的病理学和流行病学数据进行汇总分析。对1917年至1951年出生并居住在中国宣威的农民进行的一项回顾性队列研究表明，每年使用有烟和无烟煤的吨数和寿命与肺炎死亡率呈正相关，炉灶改进与肺炎死亡率降低50%和男性肺癌死亡率降低风险相关（风险比（HR）=0.62，95%置信区间（CI）=0.46-0.82）和女性（HR=0.41，95% CI=0.29-0.57）。中国宣威的一项病例对照研究评估了不同煤种的肺癌风险，发现该地区使用不同煤种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. bBladder 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 casecontrol 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 are refining metrics to evaluate agricultural pesticide use near residences, using information about the current and historical location of crops near homes. 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. Further validation of this dosimetry technique is ongoing. 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.