Serologic precursors of cancer. I. Prediagnostic serum nutrients and colon cancer risk.

A study was undertaken to determine whether prediagnostic serum levels of retinol, beta-carotene, vitamin E, and selenium are lower in colon cancer cases compared with matched, population-based controls. Sera were available from 25,802 participants of a serum collection campaign conducted in Washington County, Maryland in 1974. The authors identified from these participants 72 white colon cancer cases, who were first diagnosed with colon cancer during 1975-1983, and 143 white, living, cancer-free controls, matched to cases on the basis of age, sex, month of serum collection, and enumeration in a 1975 private census of Washington County. The mean values of serum nutrients in cases and controls, respectively, were 59.1 micrograms/dl and 61.8 micrograms/dl for retinol (p = 0.22), 32.9 micrograms/dl and 34.4 micrograms/dl for beta carotene (p = 0.52), 1.17 mg/dl and 1.27 mg/dl for vitamin E (p = 0.10), and 11.0 micrograms/dl and 11.5 micrograms/dl for selenium (p = 0.07). There were no consistent trends in the relative odds of colon cancer by quintiles of serum levels for any of the nutrients; however, a relative odds of 3.2 (95% confidence interval = 1.1-8.7) was found when persons in the four lowest quintiles of retinol were compared with those in the highest. No interactions with matching factors or between serum nutrients and no confounding effects of covariables were identified through conditional logistic regression analysis. The findings of this study do not support a strong association of low serum levels of retinol, beta-carotene, vitamin E, and selenium with an increased risk of subsequent colon cancer.

Conjunctival transdifferentiation induced by systemic vitamin A deficiency in vascularized rabbit corneas.

Conjunctival transdifferentiation, the process in which conjunctival epithelium transforms into a cornea-like epithelium with the loss of goblet cells during the healing of a total corneal epithelial defect, can be retarded or reversed by corneal neovascularization. We have previously shown that this process normally occurring on non-vascularized corneas can be retarded or reversed by topical retinoids, suggesting that vitamin A may be one of the factors from blood circulation which is responsible for modulating transdifferentiation. Herein, we have examined the effect of systemic vitamin A deficiency on vascularized corneas starting 4 months after epithelial denudation, and compared this deficient group with their vascularized and non-vascularized controls. Mean serum retinol level (microgram/dl) (n = 4) measured by HPLC was gradually reduced from 83 of the controls to 20 in a 10 month follow-up. Topographical analysis disclosed a centrifugal loss of goblet cell density with time. Histology showed complete transdifferentiation in vascularized areas at 9 months, initiated by the loss of mucin contents from receding zones first noted at 2 months. Using impression cytology, all corneas were not keratinized and all conjunctivas maintained a normal goblet cell density at 10 months. These results indicate that conjunctival epithelium on corneal surface is more sensitive to the decrease of serum vitamin A levels than that on conjunctiva, and support the hypothesis that the relative vitamin A deficiency on vascularized corneas can also result in the conjunctival transdifferentiation.

Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer.

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Population: demographic and anthropometric characteristics.

A study was designed to compare nutritional and metabolic parameters on subjects with a spectrum of vegetarian and nonvegetarian dietary patterns. The method of selection of the study population, the description of its characteristics, and the data collection protocol are described. Anthropometric measurements of vegetarians and nonvegetarians are reported and compared with previously reported measurements on similar populations.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Nutrient intake.

A 3-day diary with portion sizes weighed by the subject and a 24-h recall were obtained on 50 sets of subjects: Seventh-day Adventist lacto-ovo-vegetarians and nonvegetarians, and general population nonvegetarians, matched on age (+/- 5 yr), sex, marital status, education, type of milk preferred, and an index of the frequency of dairy and egg product use. An additional 18 unmatched persons who follow a pure vegetarian dietary pattern (use no meat, fish, fowl, dairy, or egg products) were recruited into the study. The rational for the dietary methods used is presented and details of each of the methods used are given. The results of the nutrient analysis of the 24-h recall and 3-day diary are presented. The 3-day nutrient intake means for the four groups are compared to the sex-specific recommended daily allowance both with and without supplements. The contribution of nutritional supplements to the nutrient intake is discussed. All groups show adequate or excess intake levels of calories, protein, and fat when either the 24-h recall or the 3-day diary values are considered. The higher intake of calories noted among nonvegetarians can be explained by a higher intake of both fat and protein in these groups. A, B, and C vitamin levels (3-day dairy estimates) are adequate both with and without supplements. Calcium intake is much below recommended levels for pure vegetarian females. Iron intake is low for all females. A heme iron source does not improve the intake levels for nonvegetarian females. A comparison of these results with prior reports of nutrient intake among Seventh-day Adventists is presented.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Laboratory analysis of 3-day composite of food samples.

In a study designed to characterize dietary patterns of vegetarian and nonvegetarian populations, chemical analysis of 3-day composite food samples showed lower fat content of food of vegetarians than that of nonvegetarians; pure vegetarians had the lowest. Unsaturated fatty acids were highest in the food of the pure vegetarian group. No significant difference was seen in percentage protein of the food consumed by male vegetarians and nonvegetarians while the food of female vegetarians was of lower protein content than that of the nonvegetarians. The relationship of these findings to the lower incidence of colon cancer in vegetarian populations remains to be determined.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Selected biochemical parameters in blood and urine.

Selected biochemical parameters (serum protein, albumin, prealbumin, total retinol-binding protein, vitamins A and E, total carotenoids, and urinary urea and creatinine) were determined in healthy, free-living vegetarian and nonvegetarian subjects. The groups studied were composed of Seventh-day Adventist pure vegetarians, Seventh-day Adventist lacto-ovo vegetarians, Seventh-day Adventist nonvegetarians, and general population nonvegetarians. No values indicative of nutritional deficiencies were observed in any of the subjects. Serum carotenoid levels were significantly higher in Seventh-day Adventist pure vegetarians than in members of the other groups. Mean values for serum vitamin A showed no differences between the dietary groups, although 41% of general population nonvegetarian subjects (the group considered at highest risk for colon cancer) had serum vitamin A levels in the upper quartile of the distribution. From these data no conclusions can be drawn relating to the role of dietary habits as determinants of colon cancer risk.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Concordance of nutrient information obtained by different methods.

Data obtained from two vegetarian and two nonvegetarian populations by 24-h diet recall, 3-day weighed diet diary, analysis of 3-day composite food samples, and measurement of certain biochemical parameters were compared. Correlations for group means (both sexes combined) for values obtained by 24-h recall versus 3-day diet diary were protein, r = 0.96 and total calories r = 0.86. For 3-day diet diary with food analysis, protein r = 0.89, fat r = 0.90 and for reported protein intake with serum prealbumin r = 0.74, with urinary urea nitrogen r = 0.87. Correlations were low for comparisons of means of male groups for most parameters. Individual correlations for reported protein intake and biochemical parameters were lower for males than for females. This suggests that male subjects may require special attention to insure accuracy of reporting and specimen collection. These findings indicate comparability of data from 24-h recall and 3-day diary, and agreement of dietary records with certain biochemical parameters. Protein and fat intake as determined from chemical analysis of a composite food sample correlated well (r = 0.89; r = 0.90) with that calculated from food tables.

A radiometric microbiologic assay for the biologically active forms at niacin.

A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced 14CO2 from L-[U-14C] hr malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 micrograms niacin/ml RBC (mean = 15.27 +/- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.

Free amino acids in plasma and tissue of rats born to underfed dams.

Amino acids were determined in plasma, muscle, and liver tissues of adult male rats born of mothers on restricted or nonrestricted diets during pregnancy and lactation. The concentrations of plasma alanine, glutamic acid, glycine, proline, arginine, and valine were significantly lower in the progeny of restricted mothers as compared to non-restricted mothers. Similar changes were observed in liver tissues. The concentrations of free amino acids in muscle of the perinatally malnourished progeny, however, did not differ significantly from those of the controls. The differences determined in this study are of special significance in view of the fact that the animals studied had been maintained on an adequate diet since weaning. The demonstrated effect of the maternal diet on the plasma aminogram of the off-spring some months later must be considered when interpreting plasma aminograms in studies of malnourished children.