Ellen F. Heineman

Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference

Meats cooked at high temperatures (frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well‐done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. We conducted a population‐based case‐control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n = 176) and esophagus (n = 143) between July 1988 and June 1993 and 502 controls. The dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. High intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. after excluding those who reported usually barbecuing/grilling, a source of both PAHc and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. Int. J. Cancer, 71:14–19, 1997.

Nutrient Intakes and Adenocarcinoma of the Esophagus and Distal Stomach

We studied the relationship between nutrient intakes and adenocarcinoma of the esophagus and distal stomach among 124 esophageal adenocarcinoma cases, 124 distal stomach cancer cases, and 449 controls in a population-based case-control study in eastern Nebraska. The residual method was used to adjust nutrient intake quartiles or tertiles for energy intake. We observed significant inverse associations with risk of esophageal adenocarcinoma for dietary intakes of total vitamin A [highest vs. lowest quartile, multivariate odds ratio (OR) = 0.5, P for trend = 0.05], β-cryptoxanthin (OR = 0.5, P = 0.05), riboflavin (OR = 0.5, P = 0.01), folate (OR = 0.5, P = 0.03), zinc (OR = 0.5, P = 0.05), dietary fiber (OR = 0.5, P = 0.05), protein (OR = 0.5, P = 0.02), and carbohydrate (OR = 0.4, P = 0.02). For distal stomach cancer, only vitamin C (OR = 0.6, P = 0.04), dietary fiber (OR = 0.4, P = 0.007), and carbohydrate (OR = 0.4, P = 0.004) were inversely associated with risk. Our analyses showed significant interaction between dietary fat intake, but not intakes of other nutrients, and respondent type for both cancer sites. Subgroup analyses among self-respondents revealed positive associations between saturated fat intake and risk of esophageal adenocarcinoma (OR = 1.0, 4.1, and 4.6 for intake tertiles, P for trend = 0.02) and risk of distal stomach cancer (OR = 1.0, 1.2, and 3.6, P = 0.03). However, no such associations were found among proxy respondents. Our data suggest that greater intake of dietary fiber, certain carotenoids, and vitamins may decrease the risk of esophageal adenocarcinoma, whereas greater intake of saturated fat may increase the risk of esophageal adenocarcinoma and distal stomach cancer.

Diet and risk of adult glioma in eastern Nebraska, United States.

Objective: To investigate potential associations between diet and adult glioma. Methods: We conducted a population-based case–control study of adult glioma in eastern Nebraska. Nutrient and food group intakes were estimated for 236 glioma cases and 449 controls using information obtained from a food-frequency questionnaire. Results: After adjusting for potential confounders, inverse associations with risk of adult glioma were observed for intakes of dark yellow vegetables (highest quartile versus lowest: OR = 0.6, ptrend = 0.03) and beans (OR = 0.4, ptrend = 0.0003), but no associations were seen for dietary sources of preformed nitrosamines or high-nitrate vegetables. Our nutrient analysis revealed significant inverse associations between risk of adult glioma and dietary intake of pro-vitamin A carotenoids (highest quartile versus lowest: OR = 0.5, ptrend = 0.005), α-carotene (OR = 0.5, ptrend = 0.01), β-carotene (OR = 0.5, ptrend = 0.01), dietary fiber (OR = 0.6, ptrend = 0.048) and fiber from beans (OR = 0.5, ptrend = 0.0002). We observed no significant associations with risk of adult glioma for intakes of other nutrients or compounds including nitrate, nitrite, vitamin C, vitamin E, saturated fat, cholesterol, dietary fiber from grain products, or fiber from fruit and vegetables. Conclusion: Our study does not support the N-nitroso compound hypothesis, but suggests potential roles for carotenoids and possibly other phytochemicals in reducing risk of adult glioma.

Occupational risk factors for cancer of the Central Nervous System (CNS) among US women

BACKGROUND In a recent report, we found an elevated risk of cancer of the central nervous system (CNS) in several occupations and industries, and a modest association with exposure to solvents and to contact with the public. METHODS To further explore the occupational risk of CNS cancer among women, we extended the analysis of the previous death certificate-based case-control study, including 12,980 female cases (ICD-9 codes 191 and 192) in 24 US states in 1984-1992 and 51,920 female controls who died from diseases other than malignancies and neurological disorders. We applied newly designed job-exposure matrices for 11 occupational hazards, previously reported as brain cancer risk factors, to the occupation and industry codes in the death certificates. We also conducted a separate analysis of 161 meningioma cases (ICD-9 codes 192.1 and 192.3), a tumor more frequent among women, particularly in the postmenopausal age group. RESULTS Overall, CNS cancer risk showed a 20-30% increase among women exposed to electromagnetic fields (EMF), methylene chloride, insecticides and fungicides, and contact with the public. Risk for meningioma was elevated among women exposed to lead (OR = 1.9; 95% CI 1.0, 3.9). CNS cancer did not show a clear pattern of risk increase by probability and intensity of exposure to any of the explored risk factors. Cross-classification by probability and intensity of exposure did not reveal any significant trend. Cases were too few to explore trends of meningioma by probability and intensity of exposure to lead. CONCLUSIONS We did not find evidence of a strong contribution of 11 occupational hazards to the etiology of CNS cancer. However, limitations of the occupational information might have reduced our ability to detect clear patterns of risk.

Questionnaires for Collecting Detailed Occupational Information for Community-Based Case Control Studies

In case control studies, collection of information on the workplace environment has generally been limited to self-reports of exposures or to job title, type of employer, and the dates the jobs were held, supplemented sometimes by work activities. This information, however, may be insufficient to assess the potential and level of exposure accurately due to recall difficulties and the variability of exposures within a job. A solution to this problem is to use job-specific questionnaires. The organization of a series of such questionnaires developed for a case control study of brain tumors is described. Three types of questionnaires, or modules, were developed, task-based, industry-based, and modules based on jobs with nonspecific types of tasks (e.g., laborer). The format of these modules starts with questions on the general work environment (type of employer) and proceeds to questions on tasks. More detailed information is then gathered on materials and equipment used, sensory descriptions, dermal exposure, work practices, engineering controls, and personal protective equipment use. The questionnaires cover a wide variety of exposures including solvents, heavy metals, polycyclic aromatic hydrocarbons, machining fluids, electromagnetic frequency fields, and many other exposures and, therefore, can be used in other case control studies.

Brain cancer and occupational exposure to lead.

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.

Effects of three features of a job-exposure matrix on risk estimates.

We tested the impact of three features of a job-exposure matrix on risk estimates in a case-control study that evaluated the association of methylene chloride and astrocytic brain cancer. These features were probability of use of the agent; the consideration of decade of predominant use of methylene chloride within each occupation; and the use of a more specific industrial-occupational coding system. We compared the risk estimates obtained with and without these features. The introduction of each feature had a striking effect on the estimate of relative risk. The odds ratio ranged from 1.47 with none of these features, to 2.47 with high probability of exposure within industry and occupation, to 4.15 with high probability of exposure and specific industrial-occupational coding, to 6.08 with the three features together. These results indicate that the degree of exposure misclassification can be reduced by the introduction of these features into the job-exposure matrix.

Agricultural pesticide use and risk of glioma in Nebraska, United States

Background: To evaluate the risk of the adult glioma associated with farming and agricultural pesticide use, the authors conducted a population based case control study in eastern Nebraska. Methods: Telephone interviews were conducted with men and women diagnosed with gliomas (n = 251) between 1988 and 1993 and controls (n = 498) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds upon reaction with nitrite). Non-farmers were used as the reference category for all analyses. Results: Among men, ever living or working on a farm and duration of farming were associated with significantly increased risks of glioma (⩾55 years on a farm OR = 3.9, 95% CI 1.8 to 8.6); however, positive findings were limited to proxy respondents. Among women, there were no positive associations with farming activities among self or proxy respondents. Specific pesticide families and individual pesticides were associated with significantly increased risks among male farmers; however, most of the positive associations were limited to proxy respondents. For two herbicides and three insecticides, use was positively associated with risk among both self and proxy respondents. Based on a small number of exposed cases, ORs were significantly increased for the herbicides metribuzin (OR = 3.4, 95% CI 1.2 to 9.7) and paraquat (OR = 11.1, 95% CI 1.2 to 101), and for the insecticides bufencarb (OR = 18.9, 95% CI 1.9 to 187), chlorpyrifos (OR = 22.6, 95% CI 2.7 to 191), and coumaphos (OR = 5.9, 95% CI 1.1 to 32). Conclusion: The authors found significant associations between some specific agricultural pesticide exposures and the risk of glioma among male farmers but not among female farmers in Nebraska; however, most of the positive associations were limited to proxy respondents. These findings warrant further evaluation in prospective cohort studies where issues of recall bias are not a concern.

Occupational risk factors for cancer of the central nervous system: A case‐control study on death certificates from 24 U.S. states

The risk of cancer of the central nervous system (CNS) by industry and occupation was investigated with a case-control analysis of the death certificates of 28,416 cases and 113,664 controls, selected from over 4.5 million deaths in 24 U.S. states between 1984 and 1992. Industries showing consistent increases in risk by gender and race included textile mills, paper mills, printing and publishing industries, petroleum refining, motor vehicles manufacturing, telephone and electric utilities, department stores, health care services, elementary and secondary schools, and colleges and universities. CNS cancer risk was increased for administrators in education and related fields, secondary school teachers, and other education- and health-related occupations. The application of job-exposure matrices to the industry/occupation combinations revealed a modest increase in risk for potential contact with the public at work and exposure to solvents. Occupational exposure to electromagnetic fields (EMF) was not associated with CNS cancer, although an association was observed with a few EMF-related occupations and industries. Agricultural exposures were associated with significant risk increases among white women and white men. Further work is required to investigate in more detail specific occupational exposures or possible confounders responsible for the observed associations.

Occupational risk factors for brain tumors among women in Shanghai, China

The etiology of brain cancer is not well understood and few studies have evaluated occupational risk factors among women. We evaluated occupation and industry at time of diagnosis for 276 incident primary brain tumor cases among women in Shanghai, China, for the period 1980–1984, identified through the Shanghai Cancer Registry. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were calculated for all occupations and industries with at least three female cases. SIRs compared observed to expected numbers of cases, based on incidence rates for Shanghai and the number of women in each occupation and industry according to the 1982 census. Statistically significant excesses of brain tumors were seen among grain farmers (SIR = 6.5, 95% CI = 1.3–19.1), rubber workers (SIR = 5.0, 95% CI = 1.6–11.6), and workers in transportation equipment manufacture and repair (SIR = 2.3, 95% CI = 1.1–4.3). Risks among textile spinners and winders were of borderline significance (SIR = 1.7, 95% CI = 1.0–2.8). Elevated but nonsignificant risks of 2.0 or greater were seen among nurses, plastic products workers, sanitation workers, painters, and workers in manufacture of equipment for electrical generation, transmission, and distribution. Results for farmers, rubber workers, and painters are consistent with previously reported excesses among these occupations in men. The increase among nurses is a new finding, although elevated risks have been observed among male medical professionals. Risks were elevated with likely exposure to pesticides, particularly among those thought to have a high probability and a high level of exposure (SIR = 3.6, 95% CI = 1.2–8.5).