Leonard M. Schuman

Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood

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.

THE EFFECT OF FECAL OCCULT-BLOOD SCREENING ON THE INCIDENCE OF COLORECTAL CANCER

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 study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)

Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietaryanalyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy.

The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979).

Information was collected on 301 cases of the Wiskott-Aldrich syndrome in the United States and Canada Examination of available medical records, death certificates and published case reports on these patients showed that they came from a wide geographic area and many diverse ethnic and racial groups. No significant difference was found in the incidence of cases born between 1947 and 1976; the overall rate was 4.0 per million live male births in the United States. Median survival has increased with time from eight months for patients born before 1935 to 6.5 years for those born after 1964. Seventy-six of the 301 patients (25%) were still alive at last follow-up and ranged in age from 1 to 36 years with a median of 10 years. Causes of death were primarily limited to infections or bleeding, but malignancy represented a significant problem. Twelve percent of the group (36 of 301) developed malignancy, the predominant types being lymphorecticular tumors (23 of 36) and leukemia (7 of 36). The overall relative risk for malignancy was found to be greater than 100 times that of the general population and was found to increase with increasing age.

Risk factors for colorectal cancer in a prospective study among U.S. white men

The association of diet, smoking/drinking and occupation with subsequent risk of fatal colorectal cancer was investigated in a cohort of 17,633 white males aged 35 and older, who completed a mail questionnaire in 1966. During the subsequent 20 years of follow‐up, 120 colon cancer and 25 rectal cancer deaths were identified. Due to small numbers, no significant dose‐response trends were observed in the study, but risk of colon cancer was elevated among heavy cigarette smokers (≥30/day; RR = 2.3, 95% CI 0.9–5.7), heavy beer drinkers (≥14 times/month; RR = 1.9, 95% CI 1.0–3.8) and white‐collar workers (RR = 1.7, 95% CI 1.0–3.0) or crafts workers within service and trade industries (RR = 2.6, 95% CI 1.1–5.8). In addition, an increased risk was seen for those who consumed red meat more than twice a day (RR = 1.8, 95% CI 0.8–4.4). Risk patterns for cancers of the colon and rectum combined were similar to those reported for cancer of the colon, but the estimates were somewhat dampened. Our findings support previous reports that a high intake of red meat and a sedentary life‐style may increase the risk of colon cancer. Int. J. Cancer77:549–553, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

The earlier detection of colorectal cancers. A preliminary report of the results of the occult blood study

A long‐term clinical study is underway to evaluate the merit of occult stool blood testing in the earlier detection of colorectal cancers; 48,000 participants have been enrolled. Thus far, 873 patients with occult stool blood have been examined, and 77 gastrointestinal cancers have been found in 74 patients. Although data from the control group are not yet available for comparison, most of the cancers found appear to be relatively early in their development. Conventional barium‐enema examinations were noted to have “missed” one third of the colon cancers and two‐thirds of the colon polyps which were found on colonoscopy. Preliminary results of the study appear encouraging. Definitive analysis will await the availability of additional pertinent data.

Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma.

To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkins lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkins disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.

Sensitivity, specificity, and positive predictivity of the Hemoccult test in screening for colorectal cancers. The University of Minnesota's Colon Cancer Control Study.

Data are presented on the sensitivity, specificity, and positive predictivity of the Hemoccult test based on the experience of the Minnesota Colon Cancer Control Study, a randomized clinical trial to determine whether the use of the Hemoccult test can reduce mortality from colorectal cancer. Rehydrating the slides with a drop of water before processing resulted in an increase in positivity (2.4% to 9.8%), and sensitivity (80.8% to 92.2%) but a decrease in specificity (97.7% to 90.4%) and positive predictivity (5.6% to 2.2%). The effects of age and sex were also evaluated. The test was less specific for men than women (p = 0.03). Specificity was highest for those less than 60 yr of age and decreased with increasing age (p = 0.05). The positive predictivity increased with age from 1.6% for those under 60 yr to 3.6% for those over 70 yr (p = 0.0004).

Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma.

Population-based case-control interview studies of 622 White men with non-Hodgkins lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR]=1.4), high-grade lymphoma (OR=2.3), and unclassified lymphoma (OR=2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkins lymphoma.

Nutrients and pancreatic cancer: a population-based case-control study

A case-control study was conducted in the Minneapolis-St Paul (Minnesota, United States) area to assess the role of dietary factors in the etiology of pancreatic cancer. Cases were White males aged 40 to 84 whose death certificate listed pancreatic cancer (exocrine only). White male controls were ascertained through random-digit dialing. Family members were interviewed about the subjects dietary usage in the two years prior to death (cases, n=212) or prior to interview (controls, n=220). Energy-adjusted,nutrient-intake, risk estimates were calculated. Among all respondents, negative trends were observed for polyunsaturated fat, linoleic acid, vitamin C, and β-carotene. Positive trends were observed for riboflavin and retinol. Point estimates were, in general, comparable between the analyses of all respondents and spouse-only respondents. The nutrients associated with a decreased risk for pancreatic cancer occur primarily in vegetables and fruits, of which the consumption of cruciferous and β-carotene-rich vegetables and citrus fruits provided the greatest reduction in risk.