Cancer Risk and Environmental Exposures to Nitrate, Pest

研究了环境中农业化学品致癌的危险因素，以估计这些环境暴露对农村人口癌症的贡献。农业地区的农村人口在饮用水中接触杀虫剂和硝酸盐的程度介于职业接触群体和一般人口之间。对非霍奇金淋巴瘤和脑癌、膀胱癌、结肠癌、直肠癌、胃癌、食道癌、胰腺癌和肾癌进行了病例对照研究。在这些病例对照研究中，为例行监测目的收集的水污染物数据库被用来估计过去通过公共供水对个人的接触。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。然而，较高的饮食亚硝酸盐摄入量与胰腺癌的风险增加有关。总的来说，饮用水中的硝酸盐含量与患结肠癌和直肠癌的风险无关；然而，亚硝化能力增加的特定亚组患结肠癌的风险增加。内布拉斯加州公共供水中硝酸盐含量升高与患神经胶质瘤的风险无关。内布拉斯加州公共饮用水中硝酸盐含量升高与非霍奇金淋巴瘤风险增加有关。最近在爱荷华州、西雅图、洛杉矶和底特律地区四个中心完成的非霍奇金淋巴瘤病例对照调查证实了这一假设。公共供水的硝酸盐监测数据与1960年以来的水源历史有关。在接受采访的家庭中测量了私人水井的硝酸盐含量。我们将大多数分析限制在自1960年以来硝酸盐估计占其人年的70%的人群（181例，142例对照）。我们发现，与平均饮用水硝酸盐最高四分位数（>2.90 mg/L硝酸盐- n: OR=1.2, 95% CI 0.6-2.2）或>5mg/L（10年以上：OR=1.4, 95% CI 0.7-2.9）没有总体关联。我们没有看到饮用水硝酸盐暴露与维生素C摄入量或红肉摄入量之间相互作用的证据，维生素C和红肉分别是体内NOC形成的抑制剂和前体。膳食硝酸盐与NHL风险呈负相关（最高四分位数OR=0.54, 95% CI 0.34-0.86）。饮食中亚硝酸盐的摄入与风险增加相关（最高四分位数OR=3.1, 95% CI 1.7-5.5），主要是由于摄入的面包和谷物来源的亚硝酸盐。在对内布拉斯加州和科罗拉多州普拉特河谷的人口普查群体进行的生态学研究中，硝酸盐作为癌症风险因素的问题正在得到进一步的探讨，那里的硝酸盐水平是全国最高的。利用土地覆盖、牲畜饲养场位置、土壤类型和其他信息来估计私人水井中的硝酸盐水平。我们还在开发新的方法，并改进现有的方法，在一般环境暴露研究中进行暴露评估，主要侧重于农药和硝酸盐。需要这些更好的方法来更好地估计风险，并发现在此类研究中经常遇到的相对较小的风险增加。目前正在利用地理信息系统开发新的方法来估计农药的间接接触和估计私人水井中硝酸盐的接触。利用遥感数据（卫星图像）和历史记录来估计内布拉斯加州和爱荷华州的人口，因为他们的家靠近农药处理过的农田，可能暴露于农业农药。首先，内布拉斯加州的一项可行性研究表明，可以利用现有数据和地理信息系统制作准确的历史作物地图，并将这些数据与农药使用数据联系起来，以估计间接接触农业农药的可能性。

Risk factors for cancer from agricultural chemicals in the ambient environment are studied to estimate the contribution of these environmental exposures to cancer in the rural population. Rural populations in agricultural areas have exposures to pesticides and nitrates in drinking water that are intermediate between occupationally-exposed groups and the general population. Case-control studies have been conducted on non-Hodgkin's lymphoma and cancers of the brain, bladder, colon, rectum, stomach, esophagus, pancreas, and kidney. Databases of water contaminants, gathered for routine monitoring purposes, are being used to estimate past exposures via public water supplies to individuals in these case-control studies. Nitrate levels in public water supplies in Iowa were not associated with risk of bladder and pancreas cancer. However, higher intakes of dietary nitrite were associated with an increased risk of pancreas cancer. Overall, drinking water nitrate levels were not associated with risk of colon and rectal cancer; however, specific subgroups with increased nitrosation ability were at increased risk of colon cancer. Elevated nitrate in public water supplies in Nebraska was not associated with risk of glioma. Elevated nitrate levels in public drinking water supplies were associated with an increased risk of non-Hodgkin's lymphoma in Nebraska. This hypothesis was investigated in a recently completed case-control investigation of non-Hodgkin's lymphoma in four centers: Iowa, Seattle, Los Angeles and the Detroit area. Nitrate monitoring data for public supplies was linked to water source histories from 1960 onwards. Private wells at interview homes were measured for nitrate. We limited most analyses to those with nitrate estimates for >70% of their person-years since 1960 (181 cases, 142 controls). We found no overall association with the highest quartile of average drinking water nitrate (>2.90 mg/L nitrate-N: OR=1.2, 95% CI 0.6-2.2) or with years >5mg/L (10+ years: OR=1.4, 95% CI 0.7-2.9). We saw no evidence of an interaction between drinking water nitrate exposure and either vitamin C intake or red meat intake, an inhibitor and precursor, respectively, of in vivo NOC formation. Dietary nitrate was inversely associated with risk of NHL (highest quartile OR=0.54, 95% CI 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile OR=3.1, 95% CI 1.7-5.5), largely due to intakes of bread and cereal sources of nitrite. The issue of nitrate as a cancer risk factor is being pursued further in an ecologic study of census-block groups in the Platte River Valley of Nebraska and Colorado, where elevated nitrate levels are among the highest in the country. Nitrate levels in private wells are being estimated using data on land cover, livestock feedlot locations, soil type, and other information. We are also developing new approaches, and improving existing methods, of exposure assessment in studies of general environmental exposures, with a primary focus on pesticides and nitrate. These better methods are required to better estimate risk and to detect the relatively small increases in risk often encountered in such studies. Geographic information systems (GIS) are being utilized for developing new approaches to estimating indirect exposure to pesticides and for estimating exposure to nitrate in private wells. Remote sensing data (satellite imagery) and historical records were used to estimate the population in Nebraska and Iowa potentially exposed to agricultural pesticides through the proximity of their homes to agricultural land treated with pesticides. First, a feasibility study in Nebraska demonstrated that using available data and a GIS accurate historical crop maps could be produced and that these could be linked to pesticide use data to estimate probabilities of indirect exposure to agricultural pesticides.