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.
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| Schenk, M; Schwartz, A G; O'Neal, E et al. (2001) Familial risk of pancreatic cancer. J Natl Cancer Inst 93:640-4 |
