A case-control study of tobacco use and other non-occupational risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma (United States).

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) encompasses diverse subtypes, and analyzing NHL as a single outcome may mask associations. In a new approach we evaluated associations with subtypes defined by the t(14;18) translocation, reasoning that cases within these subtypes would have more common risk factors than all NHL combined. METHODS: Archival biopsies from cases in a population-based NHL study were assayed for t(14;18) using polymerase chain reaction amplification. Exposures in 68 t(14;18)-positive and 114-negative cases were compared with 1245 controls. The expectation-maximization algorithm was used to fit polytomous regression models based on all available information, including data from 440 unclassified cases. RESULTS: Family history of hemolymphatic cancer was associated with t(14;18)-negative NHL (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.4 3.9). but not t(14;18)-positive NHL. Cigarette smoking was weakly associated with t(14;18)-positive NHL (OR 1.7, CI 0.9-3.3), but ORs decreased as smoking increased. Chewing tobacco was associated with t(14;18)-positive NHL, particularly when used before age 18 (OR 2.5. CI 1.0-6.0, 13 exposed cases). Odds ratios for both case-subtypes were doubled among hair-dye users. CONCLUSIONS: Cigarette smoking was not clearly associated with t(14;18)-positive NHL. Family history may be a marker for factors that act specifically through t(14;18)-negative pathogenic mechanisms.

Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma.

The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% CI = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% CI = 1.0-2.8), and fungicides (OR 1.8, 95% CI = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research.

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.

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 (> or = 30/day; RR = 2.3, 95% CI 0.9-5.7), heavy beer drinkers (> or = 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.

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. Dietary analyses 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.

Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study.

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.

Alcohol consumption and risk of leukemia, non-Hodgkin's lymphoma, and multiple myeloma.

Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors.

Is cigarette smoking a risk factor for non-Hodgkin's lymphoma or multiple myeloma? Results from the Lutheran Brotherhood Cohort Study.

Among 17,633 U.S. white male insurance policy holders whose use of tobacco was characterized in a 1966 self-administered questionnaire, there were 49 deaths from non-Hodgkin's lymphoma (NHL) and 21 from multiple myeloma (MM) during a 20-year follow-up. Men who had ever smoked cigarettes had an elevated mortality from NHL (RR = 2.1; CI = 0.9-4.9), with risk almost four-fold greater among the heaviest smokers (RR = 3.8; CI = 1.4-10.1) compared with those who used no tobacco. In contrast, risk of MM was only slightly elevated among those who had ever smoked cigarettes (RR = 1.3; CI = 0.4-3.9) and without evidence of a dose-response trend. Since this is the first cohort study suggesting a link between cigarette smoking and NHL and findings from case-control studies have been inconsistent, additional clarification should be sought from larger incidence-based cohort investigations.

A cohort study of tobacco use, diet, occupation, and lung cancer mortality.

In 1966, a cohort of White males aged 35 or over, who were policy-holders with the Lutheran Brotherhood Insurance Society (United States), completed a mail questionnaire on tobacco use, diet, and demographic characteristics. During the 20 years of follow-up, 219 lung cancer deaths occurred. Besides the strong relationship with cigarette smoking, we observed an effect on lung cancer risk among current users of cigars or pipes who were nonsmokers of cigarettes (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 1.0-12.6) or who were past/occasional users of cigarettes (RR = 2.7, CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were found among craftsmen and laborers, with the highest risks among subjects who worked in the mining or manufacturing industry. No association between current (as of 1966) use of beer or hard liquor and lung cancer was observed, although past users were at elevated risk. An inverse association between lung cancer and intake of fruits was observed, and risks of lung cancer were lower among persons in the highest dietary intake quintiles of vitamins A and C. Except for oranges, however, none of the inverse associations with fruits or dietary nutrients had statistically significant trends. The findings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possibly protective effect of dietary factors on lung cancer risk.

Smoking and risk of leukemia.

The relation between tobacco use and leukemia was evaluated in a population-based case-control study of 578 white men with leukemia and 820 controls conducted in Iowa and Minnesota during 1981-1984. Risks were significantly elevated for all leukemia (odds ratio (OR) = 1.4) and chronic lymphocytic leukemia (OR = 1.6) for both tobacco users and cigarette smokers. There were significantly elevated risks for cigarette smokers of longest duration for all leukemia (OR = 1.6), chronic myelogenous leukemia (OR = 3.3), and chronic lymphocytic leukemia (OR = 1.6). Thus, the findings of this study provide additional support for an association between smoking and the risk of several types of leukemia.

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

Population-based case-control interview studies of 622 White men with non-Hodgkin's 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-Hodgkin's lymphoma.

Cigarette smoking and leukemia: results from the Lutheran Brotherhood Cohort Study.

In a 20-year follow-up (1966-86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR] = 2.7), and other and unspecified leukemia (RR = 1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking.

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 subject's 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 beta-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 beta-carotene-rich vegetables and citrus fruits provided the greatest reduction in risk.

A cohort study of stomach cancer in a high-risk American population.

Demographic, smoking and dietary information was obtained from a cohort of 17,633 white American men, largely of Scandinavian and German descent, who responded to a mailed questionnaire in 1966. After 20 years of follow-up, 50% to 90% increases in mortality from stomach cancer (75 deaths) were found among foreign-born, their children, and among residents of the North Central states. An association was seen with low educational attainment and laboring or semiskilled occupations, primarily among immigrants and their children. Risk was evaluated in subjects who regularly smoked cigarettes (RR = 2.6, 95% CI = 1.1 to 5.8). A significant dose-response trend was observed, with subjects who smoked 30 or more cigarettes per day having more than a five-fold increased risk compared with those who never smoked. Elevated risks were also found for pipe smoking and smokeless tobacco use, but not for alcohol consumption. Analysis of dietary consumption of nine food groups revealed no significant associations with stomach cancer. However, total carbohydrate intake and a few individual food items (salted fish, bacon, cooked cereal, milk, and apples) were associated with increased risk. The findings of this prospective study of a high-risk population add to the limited evidence relating tobacco consumption to stomach cancer risk and suggest clues to ethnic, geographic, and dietary risk factors.

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-Hodgkin's 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 Hodgkin's 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.

Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study.

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.

Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota.

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.

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).

A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet.

A pancreatic cancer case-control study was conducted in the Minneapolis-St. Paul area. Family members were interviewed about the subject's usage of cigarettes, alcohol, coffee, and other dietary factors in the two years prior to death (cases, n = 212) or prior to interview (controls, n = 220). The adjusted odds ratio for two packs or more of cigarettes per day was 3.92 (95% CI = 1.18, 13.01) and four or more drinks per day OR 2.69 (95% CI = 1.00, 7.27). Coffee was not a risk factor (seven cups or more per day; OR 0.58 (95% CI = 0.27, 1.27). A positive trend was observed for beef and pork consumption, and a negative trend from cruciferous vegetables.