Leonard M. Schuman

BACKGROUND: Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness. METHODS: We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all study participants during 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the sequential log-rank statistic. RESULTS: The 13-year cumulative mortality per 1000 from colorectal cancer was 5.88 in the annually screened group (95 percent confidence interval, 4.61 to 7.15), 8.33 in the biennially screened group (95 percent confidence interval, 6.82 to 9.84), and 8.83 in the control group (95 percent confidence interval, 7.26 to 10.40). The rate in the annually screened group, but not in the biennially screened group, was significantly lower than that in the control group. Reduced mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer. CONCLUSIONS: Annual fecal occult-blood testing with rehydration of the samples decreased the 13-year cumulative mortality from colorectal cancer by 33 percent.

BACKGROUND: Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening. METHODS: We followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to newly diagnosed cases of colorectal cancer and deaths. Follow-up has been more than 90 percent complete. RESULTS: During the 18-year follow-up period, we identified 1359 new cases of colorectal cancer: 417 in the annual-screening group, 435 in the biennial-screening group, and 507 in the control group. The cumulative incidence ratios for colorectal cancer in the screening groups as compared with the control group were 0.80 (95 percent confidence interval, 0.70 to 0.90) and 0.83 (95 percent confidence interval, 0.73 to 0.94) for the annual-screening and biennial-screening groups, respectively. For both screening groups, the number of positive slides was associated with the positive predictive value both for colorectal cancer and for adenomatous polyps at least 1 cm in diameter. CONCLUSIONS: The use of either annual or biennial fecal occult-blood testing significantly reduces the incidence of colorectal cancer.

A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for prostate cancer were significantly elevated among cigarette smokers (relative risk, 1.8; 95% confidence interval, 1.1-2.9) and users of smokeless tobacco (relative risk, 2.1; 95% confidence interval, 1.1-4.1). No significant associations were found with frequency of consumption of meats, dairy products, fruits, or vegetables. There were no overall significant associations between consumption of vitamin A from animal sources (retinol) and provitamin A from plant sources (carotene) and risk, but positive trends were seen for ages under 75, while inverse associations were found at older ages. Beverage consumption, including drinking coffee and alcohol, was unrelated to risk. Marital status, education, rural/urban status, and farming residence were also unrelated to the risk of fatal prostate cancer. The findings add to limited evidence that tobacco may be a risk factor for prostate cancer, but fail to provide clues to dietary or other risk factors.

Data from an in-person interview study of 622 white men with newly diagnosed non-Hodgkin's lymphoma and 1245 population-based controls in Iowa and Minnesota were used to measure the risk associated with farming occupation and specific agricultural exposures. Men who ever farmed were at slightly elevated risk of non-Hodgkin's lymphoma (odds ratio = 1.2, 95% confidence interval = 1.0-1.5) that was not linked to specific crops or particular animals. Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene. Associations were generally stronger for first use prior to 1965 than more recently, and when protective clothing or equipment was not used. Small risks were associated with the use of the phenoxyacetic acid herbicide 2,4-dichlorophenoxyacetic acid, but the risks did not increase with latency or failure to use protective equipment. Exposure to numerous pesticides poses problems of interpreting risk associated with a particular chemical, and multiple comparisons increase the chances of false-positive findings. In contrast, nondifferential exposure misclassification due to inaccurate recall can bias risk estimates toward the null and mask positive associations. In the face of these methodological and statistical issues, the consistency of several findings, both within this study and with observations of others, suggests an important role for several insecticides in the etiology of non-Hodgkin's lymphoma among farmers.

Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, the authors conducted a population-based case-control interview study of 578 white men with leukemia and 1245 controls living in Iowa and Minnesota. Consistent with recent mortality studies, there were slight, but significant, elevations in risk for all leukemia [odds ratio (OR) 1.2] and chronic lymphocytic leukemia (OR 1.4) for farmers compared to nonfarmers. There were no significant associations with leukemia for exposure to specific fungicides, herbicides (including 2,4-D and 2,4,5-T), or crop insecticides. However, significantly elevated risks for leukemia of greater than or equal to 2.0 were seen for exposure to specific animal insecticides including the organophosphates crotoxyphos (OR 11.1), dichlorvos (OR 2.0), and famphur (OR 2.2) and the natural product pyrethrins (OR 3.7) and the chlorinated hydrocarbon methoxychlor (OR 2.2). There were also smaller, but significant, risks associated with exposure to nicotine (OR 1.6) and DDT (OR 1.3). This finding of elevated risks for insecticides used on animals deserves further evaluation.