DDT AND RELATED COMPOUNDS AND PANCREAS CANCER

滴滴涕及相关化合物与胰腺癌

• 批准号: 2414974
• 负责人: DAVID H GARABRANT
• 金额: $ 49.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2414974
• 关键词: blood chemistry; cancer risk; case history; chemical carcinogenesis; clinical research; dichlorodiphenyltrichloroethane; environmental contamination; family genetics; gene mutation; human population study; human subject; occupational hazard; pancreas neoplasms; questionnaires; statistics /biometry; tumor suppressor genes

DESCRIPTION: (Adapted from Investigator's Abstract) Pancreas cancer is the fifth leading cause of cancer mortality in the United States and has the poorest survival rate of all major malignancies. Risk factors for this disease remain unspecified with the exception of cigarette smoking. Although DDT was banned from use in the U.S. in 1972, DDT is still used abroad, DDT related materials are still being used in the U.S., DDT is a common environmental pollutant and persists in the food chain, and DDE (a major metabolite of DDT) persists in adipose tissue for decades after exposure. The investigators recently reported a strong association between pancreas cancer and exposure to DDT and related materials (Ethylan and DDD) among chemical manufacturing workers. The primary goals of this proposal are to follow-up this important observation to determine whether in the general population 1) serum DDE levels and exposure to DDT and related materials are risk factors for pancreas cancer, 2) markers of genetic damage (Ki-ras mutations, p53 mutations and microsatellite instability) that are associated with pancreas cancer are correlated with exposure to DDT and related materials, 3) markers of genetic damage in peripheral lymphocytes (V(D)J recombinants) that have been associated with pesticide use are correlated with exposure to DDT and related materials. These investigations will provide important insights into molecular mechanisms by which DDT may lead to pancreas cancer. The investigators propose a case-control study of pancreas cancer in which 325 people with newly diagnosed pancreas cancer will be identified in southeastern Michigan using seven participating hospitals in metropolitan Detroit and Ann Arbor. Random digit dialing will be used to identify two controls (650 total) for each case, frequency matched on age, sex, race, type of respondent and county of residence. All study participants will be administered a questionnaire to assess lifetime exposure to common pesticides from both environmental and occupational sources, family history of cancer, past medical history, smoking history, consumption of Great Lakes fish, and demographic information. We will draw blood at the time of the interview for measurement of serum lipid DDE analyses. Peripheral blood lymphocytes will also be used to study V(D)J recombinations. Pancreas cancer tissue from the cases will be obtained and studied for Ki-ras mutations and microsatellite instability. Logistic regression analyses will be conducted to explore relationships between the covariates and pancreas cancer and to estimate odds ratios and ninety-five percent confidence intervals. Relationships between serum DDE levels and self-reported DDT exposure and other covariates will be explored in multiple regression analyses. For the analyses of microsatellite instability, p53 mutations and Ki-ras gene mutations, the analyses will be limited to subjects who have pancreas cancer (because of the need for tumor tissue) and will investigate whether these genetic abnormalities are associated with serum DDE levels. For these analyses, those subjects who have the genetic abnormality will be considered to be cases and those without will be controls, then DDE levels will be compared. If the number of subjects with each genetic abnormality is small, descriptive analyses will be done rather than logistic regression. Family aggregation of pancreas cancer among the cases will be analyzed using segregation analysis to examine if the distribution of pancreas cancer in families is compatible with Mendelian genetics.

描述：（根据研究者的摘要改编）胰腺癌是 美国癌症死亡率的第五个主要原因 所有主要恶性肿瘤中最差的生存率。风险因素 除吸烟外，该疾病仍然未指定。 尽管DDT于1972年被禁止在美国使用，但DDT仍被使用 在国外，与DDT相关的材料仍在美国使用，DDT是 食物链中的一种常见环境污染物和持续存在，DDE （DDT的主要代谢物）在脂肪组织中持续数十年 接触。调查人员最近报告了牢固的关联 在胰腺癌和暴露于DDT和相关材料之间 （乙烷和DDD）在化学制造工人中。 该提案的主要目标是跟进这一重要的 观察确定一般人群中是否是）血清DDE 水平和暴露于DDT和相关材料是风险因素 胰腺癌，2）遗传损伤标记（Ki-Ras突变，p53 与 胰腺癌与暴露于DDT和相关的暴露有关 材料，3）外周淋巴细胞中遗传损伤的标记（V（d）J 与农药使用相关的重组） 与暴露于DDT和相关材料相关。这些 调查将为分子机制提供重要的见解 DDT可能导致胰腺癌。 研究人员提出了一项胰腺癌的病例对照研究 将确定有325名新诊断的胰腺癌的人 在密歇根州东南部使用七家参与的医院 大都会底特律和安阿伯。将使用随机数字拨号 要识别每种情况的两个控件（总共650个），频率匹配 关于年龄，性别，种族，被告类型和居住县。全部 研究参与者将接受调查表以评估 终生暴露于环境和环境中的常见农药 职业来源，癌症家族史，过去的病史， 吸烟史，大湖鱼的消费和人群 信息。我们将在面试时抽血 血清脂质DDE分析的测量。外周血淋巴细胞 还将用于研究V（d）J重组。胰腺癌组织 从案例中获得并研究了Ki-Ras突变和 微卫星不稳定性。 将进行逻辑回归分析以探索关系 在协变量和胰腺癌之间，以估计优势比 和百分之九十五的置信区间。之间的关系 血清DDE水平和自我报告的DDT暴露和其他协变量将 在多个回归分析中探讨。用于分析 微卫星不稳定性，p53突变和Ki-Ras基因突变， 分析将仅限于患有胰腺癌的受试者（因为 需要肿瘤组织），并将研究这些遗传 异常与血清DDE水平有关。对于这些分析， 那些患有遗传异常的受试者将被认为是 案例和没有控制的情况将是控制，那么DDE级别将是 比较的。如果每个遗传异常的受试者数量是 小规模的描述性分析将是进行的，而不是逻辑 回归。病例中胰腺癌的家庭聚集将 可以使用分离分析来检查是否分布 家庭中的胰腺癌与门德尔遗传学兼容。