Environmental factors and high risk of esophageal cancer among men in coastal South Carolina.

A case-control study involving interviews of 207 men with esophageal cancer and 422 control subjects or their next of kin was conducted to identify reasons for the unusually high rates of esophageal cancer among men in coastal South Carolina. Tobacco and alcohol, including moonshine, were identified as the major determinants of esophageal cancer risk. Increased risk was also associated with low intake of fresh fruits but not with drinking of local herbal teas. The findings suggest that efforts aimed at reducing tobacco and alcohol use will help to lower the elevated rates of esophageal cancer in coastal South Carolina.

Dietary factors in oral and pharyngeal cancer.

A population-based case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on a number of risk factors, including diet. Interviews were obtained from 871 oral cancer patients and 979 controls among whites, frequency matched for age and sex. Consumption frequency of 61 food items was assessed in the questionnaire; attention was given to foods that are sources of vitamins A and C and carotene. The major finding was an inverse relationship between fruit intake and risk of oral and pharyngeal cancer; individuals in the highest quartile of intake had about half the risk of those in the lowest quartile. Vitamin C, carotene, or fiber in fruit did not appear to account completely for this relationship, since these nutrients in vegetables did not provide similar protection. This finding suggests the influence of other constituents in fruits, although it is possible that cooking vegetables may have a nutrient-diminishing effect. Dietary intake of other nutrients, such as the B vitamins, vitamin E, folate, and iron, showed no consistent relationship to risk of oral and pharyngeal cancer. Coffee or other hot beverage consumption did not increase risk; intake of nitrite-containing meats or cooking practices, such as smoking, pickling, or charcoal grilling, also did not increase risk. All analyses were adjusted for the effects of tobacco and alcohol, strong risk factors for oral and pharyngeal cancer. Dietary findings among the few subjects who did not use tobacco or alcohol were similar to those for all subjects.

Vitamin A and other deficiencies in Linxian, a high esophageal cancer incidence area in northern China.

Biochemical analyses were conducted to evaluate the nutritional status of a high esophageal cancer risk population in Linxian, People's Republic of China. A study was conducted in September 1980 in which plasma levels of vitamins A, B2, and C were analyzed. In a second study in 1983, the plasma fat-soluble vitamins were analyzed with a newly developed high-performance liquid chromatography method that allowed the simultaneous determination of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, and lycopene in 0.1 ml of plasma sample. The average plasma retinol levels ranged from 24 to 27 micrograms/dl among the population groups, with 20-35% of the individuals having levels under 20 micrograms/dl. Low plasma beta-carotene levels averaging 8-12 micrograms/dl were observed among the population groups. Low plasma alpha-tocopherol levels with average values around 700 micrograms/dl were also observed; about half the individuals were either low or deficient in vitamin E. After 4 months of supplementation with daily multivitamin tablets, the plasma contents of retinol and alpha-tocopherol were significantly increased. The plasma alpha-carotene and beta-carotene were also increased, possibly as a reflection of seasonal changes in the diet or a sparing effect of vitamins A and E on these carotenes. Low plasma ascorbate levels with an average of 567 micrograms/dl were observed, and about 23% of the individuals had values under 200 micrograms/dl. Riboflavin deficiency was prevalent, with about 90% of the subjects having an erythrocyte glutathione activation coefficient over 1.2. The study establishes the low nutritional status in vitamins of the population in Linxian and provides the background for further studies on the effects of nutritional deficiency on carcinogenesis.

Compliance and nutritional status during feasibility study for an intervention trial in China.

As part of a pilot study to assess the feasibility of a long-term intervention trial to be done in Linxian, People's Republic of China, nutritional status and compliance were assessed in villagers taking daily multivitamin pills containing the U.S. Recommended Dietary Allowances (RDA). Before the start of the trial and again during its 4th month, nutritional status was assessed by laboratory tests and a dietary interview. Compliance was assessed in all subjects by pill counts and in a subset by urinary riboflavin loading-dose tests. At the outset of the trial, the study population had widespread biochemical and dietary deficiencies of ascorbic acid and riboflavin. As expected, subjects taking a daily pill had significantly improved status for these vitamins during the study. Compliance as measured by pill counts was excellent, with over 90% of the subjects taking at least 80% of their daily pills. Mean urinary excretion of a riboflavin loading dose entered and remained in the normal range after 3 weeks of supplementation, indicating that compliance did not fall off over time. Compliance was similar in normal subjects and in those with a prior diagnosis of esophageal dysplasia. Compliance also was nearly as good in subjects receiving monthly home visits as in those receiving weekly home visits from the barefoot doctor (village paramedical worker). The results of this pilot study indicated that a long-term intervention trial was feasible in Linxian and that the RDA dose level of vitamins was effective in ameliorating certain nutritional deficiencies prevalent in the study population.

Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia.

BACKGROUND: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia. PURPOSE: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian. METHODS: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years. RESULTS: A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups. CONCLUSIONS: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus. IMPLICATIONS: Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.

Allium vegetables and reduced risk of stomach cancer.

Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals.

Smoking, air pollution, and the high rates of lung cancer in Shenyang, China.

A case-control study involving interviews with 1,249 patients with lung cancer and 1,345 population-based controls was conducted in Shenyang, an industrial city in northeastern China, where mortality rates are high among men and women. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the lung cancers in males and 37% in females. The attributable risk percentage among females is high compared to elsewhere in China, largely because of a higher prevalence of smoking among women. After adjustment for smoking, there were also significant increases in lung cancer risk associated with several measures of exposure to air pollutants. Risks were twice as high among those who reported smoky outdoor environments, and increased in proportion to years of sleeping on beds heated by coal-burning stoves (kang), and to an overall index of indoor air pollution. Threefold increases in lung cancer risk were found among men who worked in the nonferrous smelting industry, where heavy exposures to inorganic arsenic have been reported. The associations with both smoking and indoor air pollution were stronger for squamous cell and small cell carcinomas than for adenocarcinoma of the lung. Risks due to smoking or air pollution were not greatly altered by adjustment for consumption of fresh vegetables or sources of beta carotene or retinol, prior chronic lung diseases, or education level. The findings suggest that smoking and environmental pollution combine to account for the elevated rates of lung cancer mortality in Shenyang.

Diet and high risk of stomach cancer in Shandong, China.

A case-control investigation involving interviews with 564 stomach cancer patients and 1131 population-based controls was conducted to evaluate reasons for the exceptionally high rates of stomach cancer in Linqu, a rural county in Shandong Province in northeast China. Daily consumption of sour pancakes, a fermented indigenous staple, was associated with a 30% increase in risk. Risks of stomach cancer were also increased by 2- to 3-fold among persons with prior chronic gastritis or gastric ulcer, by 80% among those with stomach cancer in a family member, by 50% among men who smoked one or more packs of cigarettes/day, by 40% among those who preferred salty foods, and by 50% among families with moldy grain supplies. In contrast, risks tended to decrease in proportion to increasing consumption of fresh vegetables and fruits. This protective effect was more pronounced for vegetables, with those in the highest quartile of intake at less than one-half the risk of those in the lowest. Stomach cancer risks also declined with increasing dietary intake of carotene, vitamin C, and calcium, but not retinol. These findings provide leads to dietary factors that contribute to the high rates in Linqu, where stomach cancer is the leading cause of cancer and has not yet begun to decline as in other parts of the world.

Separation of the dietary fat and cholesterol influences on plasma lipoproteins of rhesus monkeys.

In order to isolate the effects of the type of dietary fat from those of dietary cholesterol on the circulating pool of cholesterol, plasma lipoproteins were characterized in juvenile rhesus monkeys fed semipurified diets containing 31% of calories as corn oil or coconut oil. Half the diets contained 300 mg of cholesterol per 1000 kcal. The fatty acids of cholesteryl esters and phospholipids varied significantly with dietary fat such that saturated and monounsaturated fatty acids replaced polyunsaturated fatty acids in low-density lipoproteins (LDL) and high density-lipoproteins of rhesus monkeys fed coconut oil. Dietary cholesterol alone induced small but significant increases in the cholesteryl ester: triglyceride ratio in both very low-density lipoproteins and LDL. Whereas neither saturated fat (coconut oil) nor cholesterol alone substantially altered the plasma cholesterol concentration or lipoprotein profile, together these dietary components interacted synergistically to produce a significant elevation in plasma cholesterol. This was due primarily to a significant rise in the cholesteryl ester fraction of LDL, disproportionate to any change in LDL protein concentration. The data are consistent with current hypotheses that relate parameters of LDL turnover and clearance to their macromolecular structure and physicochemical characteristics.

Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance.

Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.

Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique.

OBJECTIVE: This study examined the accuracy of a multiple-pass, 24-hour dietary recall method for estimating energy intakes of men and women by comparing it with energy intake required for weight maintenance. DESIGN: Three-day, multiple-pass, 24-hour recalls were obtained on randomly selected days during a self-selected diet period when subjects were preparing their own meals and during a controlled diet period when all meals were provided by the study. During the dietary intervention, weight was maintained; body weight and dietary intake were monitored closely, thereby allowing estimation of the energy intake required for weight maintenance. SUBJECTS/SETTING: Seventy-eight men and women (22 to 67 years old) from the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study participated in this study. All 24-hour recalls were collected using a computer-assisted, interactive, multiple-pass telephone interview technique. Energy requirements for each individual were determined by the energy content of the DELTA study foods provided to maintain weight. STATISTICAL ANALYSIS: Paired and independent t tests were conducted to examine differences among study variables. Agreement between recalled energy intake and weight maintenance energy intake was analyzed using the Bland-Altman technique. RESULTS: Compared with weight maintenance energy intake, during the self-selected diet period men and women underestimated energy intake by 11% and 13%, respectively. During the controlled diet period, men underestimated energy intake by 13%, whereas women overestimated energy by 1.3%. APPLICATIONS/CONCLUSIONS: Men had a tendency to under-estimate energy intake irrespective of the recording period. The accuracy of the recalled energy intake of women may be influenced by recording circumstances. Researchers should examine the factors influencing underreporting and overreporting by individuals and their impact on macronutrient and micronutrient intakes. Also, strategies need to be developed to minimize underreporting and overreporting.

Diet design for a multicenter controlled feeding trial: the DELTA program. Delta Research Group.

OBJECTIVE: To describe the process and results of diet standardization, diet validation, and monitoring of diet composition, which were key components of protocol 1 of Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA-1), the initial protocol in a program of multicenter human feeding studies designed to evaluate the effects of amount and type of fat on lipoproteins and hemostasis parameters in various demographic groups. DESIGN: DELTA-1 was based on a randomized, blinded, crossover experimental design. Three diets were fed for 8 weeks to 103 healthy men and women aged 22 to 67 years at 4 field centers. Diet A, an average American diet, was designed to provide 37% of energy from fat, 16% of energy from saturated fatty acids (SFAs); diet B (step 1 diet) was designed to provide 30% of energy from fat, 9% of energy from SFA; and diet C (low SFA diet) was designed to provide 26% of energy from fat, 5% of energy from SFA. Key features of diet standardization included central procurement of fat-containing foods, inclusion of standard ingredients, precision weighing of foods--especially sources of fat and cholesterol--and use of standardized written procedures. SETTING: For menu validation, a set of 12 menus for each diet was prepared in duplicate and chemically assayed. For monitoring of diet composition during the study, an 8-day diet cycle (6 weekday and 2 weekend menus) was sampled by every field center twice during each of 3 feeding periods. STATISTICAL ANALYSES: Means (+/- standard error) were calculated and compared with target nutrient specifications. RESULTS: DELTA-1 was able to provide a standardized diet that met nutrient specifications across 4 field centers over 24 weeks of participant feeding spanning a total of 8 months. APPLICATIONS: Prestudy chemical validation of menus and continuous sampling and assay of diets throughout the study are essential to standardize experimental diets and to ensure that nutrient target goals are met and maintained throughout a controlled multicenter feeding study.

Depressed PMNC blastogenic response in patients with cancer of the head and neck: a study of IL-2 production, IL-2 consumption, and IL-2 receptor expression.

Approximately two thirds of patients with head and neck cancer have been shown to have peripheral mononuclear cells that exhibit a lowered blastogenic response to the T-cell mitogens, concanavalin A and phytohemagglutinin. To investigate the possible mechanisms of this phenomenon, we measured the amount of activated T-cell lymphokine interleukin-2 present in the supernatant of concanavalin A- or phytohemagglutinin-stimulated peripheral mononuclear cells taken from patients with squamous cell carcinoma of the upper aerodigestive tract. Concentrations were found that were similar to those of healthy subjects. The rate of interleukin-2 consumption and the degree of interleukin-2 receptor expression also were similar for patients and controls. In the course of these experiments, it was noted that differences in blastogenic response between patients and controls were abolished when, 24 hours after the beginning of either concanavalin A or phytohemagglutinin stimulation, the culture supernatant was removed and replaced by fresh medium, containing recombinant interleukin-2 to further sustain cell growth. This suggests that the lower blastogenic response found in patients with head and neck cancer is not due to global immune unresponsiveness, but instead, is caused by selective cell dysfunction(s), which may include the production of a suppressor factor following concanavalin A or phytohemagglutinin stimulation.

Nutritional status in Linxian, China: effects of season and supplementation.

The ability of a supplement to counteract seasonal alterations in nutritional status for certain vitamins was studied in Linxian, an area in northern China with high rates of esophageal cancer. 150 subjects took one daily pill from April to August (16 weeks), whereas 50 subjects did not take any supplement. Deficiencies of ascorbic acid, riboflavin, folic acid, retinol and tocopherol were prevalent at the outset of the study. The changes in diet occurring between the end of the winter (April) and the start of the autumn vegetable harvest (August) were reflected in greatly improved ascorbic acid status and slightly improved riboflavin status. Plasma retinol, tocopherol, alpha-carotene and beta-carotene were little affected by season, whereas erythrocyte folate levels declined. The ascorbic acid, riboflavin, folate, retinol and tocopherol status of the supplemented subjects was significantly improved. After 16 weeks of supplementation, erythrocyte folate levels of subjects with esophageal dysplasia were improved but remained significantly lower than those of normal supplemented subjects, targeting folic acid as a nutrient of particular interest in this precancerous condition.

Growth in black and white children with Down syndrome.

Growth in 28 black and 30 white children with Down syndrome was compared at birth, 4 months, 1 year, and 7 years. Weight, length, and head circumference measurements were taken from case records of the U.S. Collaborative Perinatal Project. A multivariate regression model was used to examine simultaneously the effects on these measurements of sex, race, presence of congenital heart disease, maternal smoking during pregnancy, and maternal weight at delivery. Results showed that black and white children with Down syndrome have essentially identical growth rates and that long-term growth of these children may be responsive to external influences, such as maternal smoking and maternal weight at delivery.

Sample size and power for case-control studies when exposures are continuous.

In estimating the sample size for a case-control study, epidemiologic texts present formulae that require a binary exposure of interest. Frequently, however, important exposures are continuous and dichotomization may result in a 'not exposed' category that has little practical meaning. In addition, if risks vary monotonically with exposure, then dichotomization will obscure risk effects and require a greater number of subjects to detect differences in the exposure distributions among cases and controls. Starting from the usual score statistic to detect differences in exposure, this paper develops sample size formulae for case-control studies with arbitrary exposure distributions; this includes both continuous and dichotomous exposure measurements as special cases. The score statistic is appropriate for general differentiable models for the relative odds, and, in particular, for the two forms commonly used in prospective disease occurrence models: (1) the odds of disease increase linearly with exposure; or (2) the odds increase exponentially with exposure. Under these two models we illustrate calculation of sample sizes for a hypothetical case-control study of lung cancer among non-smokers who are exposed to radon decay products at home.

Novel engineering approaches to obesity, overweight, and energy balance: public health needs and research opportunities.

The obesity epidemic is one of the most rapidly evolving public health problems of our day. At present, 2/3 of American adults and 1/6 of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high and reflects documented increased risk of cardiovascular disease, type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis, and increased mortality from these ailments, especially among the most obese. Innovative engineering technologies are needed to address a large range of problems in energy balance, intake, and expenditure that are associated with the obesity epidemic. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Novel sensors, devices, imaging technologies, nanotechnology, biomaterials, and other approaches need to be developed and evaluated through multidisciplinary collaborations between engineers, physical scientists, and scientists with expertise in obesity and nutrition. The goal is to encourage research to develop useful technologies and tools to facilitate research and eventually to support therapeutic advances and behavioral change. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov).

Intake of tapwater and total water by pregnant and lactating women.

BACKGROUND: Despite theoretically higher requirements for water due to physiologic demands of pregnancy and lactation, little is known of actual ranges of intake in pregnant and lactating women. METHODS: Population-based estimates of total water and tapwater intake in women of reproductive age were derived using data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non-pregnant, non-lactating control women. RESULTS: Total water intake (mean +/- SD) was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310 +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to or greater than 3,000 g/day among 7 percent of control women, 11 percent of pregnant women, and 13 percent of lactating women. Tapwater intake was equal to or greater than 2,000 g/day among 10 percent of control women, 15 percent of pregnant women, and 8 percent of lactating women. CONCLUSIONS: These results should be useful in estimating amounts of nutrients and toxic substances that women of reproductive age obtain through the water supply.

Effects of heparin on in vitro immune parameters.

The effects of heparin on several in vitro immune functions [blastogenesis, interleukin-2(IL-2) production] were investigated. The addition of heparin to human peripheral mononuclear cells stimulated with phytohemagglutinin or pokeweed mitogen significantly increased the blastogenic response of these cells. Peak IL-2 concentrations in the supernatant of heparin-containing cultures were two- to fourfold higher than in heparin-free cultures. Flow cytometry experiments revealed that Leu-M3-positive cells were the only subset to be significantly affected by heparin, which induced an increase both in number and in fluorescence intensity of Leu-M3-positive cells. In contrast, the expression of DR molecules on monocytes was slightly decreased. It is speculated that the observed antimetastatic effects of heparin may be exerted through local immunomodulation in macrophage-rich tissues.

A case-control study of esophageal cancer in Linxian, People's Republic of China.

A case-control study involving interviews with 1,200 patients with esophageal cancer and 1,200 population-based controls has been initiated in Linxian, a county in North Central China with perhaps the world's highest mortality rates for this tumor. Here we describe the rationale, study methods, and results of a pilot study that established the feasibility of the investigation.