linoleic-acid and Esophageal-Neoplasms

The incidence of squamous cancer of the esophagus varies up to a hundredfold in different regions of the world. In Transkei, South Africa, a particularly high incidence of the disease is observed. We have previously proposed an association between a maize-rich diet and elevated levels of intragastric prostaglandin E2 production (PGE(2)). Here we investigate the molecular mechanisms by which a high-maize diet could lead to increased incidence of squamous cancer of the esophagus. We confirm that levels of PGE(2) are high (606.8 pg/ml) in the gastric fluid of individuals from Transkei. We also show that treatment of esophageal cells with linoleic acid, which is found at high levels in maize and is a precursor to PGE(2), leads to increased cell proliferation. Similarly, treatment of cells with PGE(2) or with gastric fluid from Transkeians also leads to increased proliferation. Our data suggest that the high levels of PGE(2) associated with a maize-rich diet stimulate cell division and induce the enzyme COX 2, resulting in a positive feedback mechanism that predisposes the esophagus to carcinoma.

Topics: Black People; Carcinoma, Squamous Cell; Cell Line; Cell Proliferation; Cyclooxygenase 2; Diet; Dinoprostone; Disease Susceptibility; Esophageal Neoplasms; Esophagus; Feedback, Physiological; Gastric Juice; Gene Expression Regulation, Neoplastic; Humans; Linoleic Acid; Risk Factors; RNA, Messenger; Seeds; South Africa; Surveys and Questionnaires; Zea mays

Endemic cancer of the oesophagus in Africa is associated with the use of maize as the staple. In one African community endemic cancer of the oesophagus has been shown to have a strong statistical association with the consumption of foods based on maize in the meal form. A strong association with consumption of maize meal has also been shown in a region of Italy. It has been argued in the past that the association with maize consumption is due to a fortuitous association; or due to the nutritional deficiencies of maize meal; or due to fungal contamination. We argue that maize meal is a distinctly different food from whole maize, and that nutritional content as much as deficiency is responsible for predisposition of the oesophagus to carcinogenesis. An important factor is the breakdown of esterified linoleic acid to the free form in stored maize meal. This leads to excess production of prostaglandin E2 in the stomach. The excess Prostaglandin E2 causes a low-acid duodenogastro-oesophageal reflux, which predisposes to carcinogenesis. Supporting evidence is available that the steps of this mechanism occur in endemic areas, and that they are associated with the carcinogenic process. Health measures including poverty alleviation, health education, and monitoring and control of maize meal storage and content may be required to reduce the incidence of this disease in Africa.

Topics: Africa; Carcinoma, Squamous Cell; Corn Oil; Diet; Dinoprostone; Disease Susceptibility; Endemic Diseases; Esophageal Neoplasms; Fatty Acids, Nonesterified; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Incidence; Linoleic Acid; Models, Biological; Zea mays

In 1996-2004 a case-control study on nutrient intake, dietary constituents and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. In fact, Uruguay, and especially its northern provinces, which border Brazil, are high-risk areas. The study included 234 cases and 936 controls. The controls were hospitalized patients with non-neoplastic disease, which was not related to tobacco smoking and alcohol drinking, and without recent changes in their diets. Controls were frequency matched to cases on age (10-yr intervals), sex, and residence (Montevideo and other provinces). Dietary constituents were energy adjusted using the residuals method and then categorized in quartiles according to the distribution of the controls. The final model included linoleic acid, lycopene, alpha-carotene, beta-cryptoxanthin, vitamin A, monounsaturated fat, total carbohydrates, beta-carotene, and folate. The odds ratio (OR) for high intake of linoleic acid was 1.4 (95% confidence interval, CI = 1.2-1.6), whereas lycopene displayed a strong protective effect (OR = 0.7; 95% CI = 0.6-0.9). The possible role of these and other dietary constituents in esophageal carcinogenesis is discussed.

Topics: Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Confidence Intervals; Diet; Diet Surveys; Esophageal Neoplasms; Female; Humans; Linoleic Acid; Lycopene; Male; Middle Aged; Odds Ratio; Risk Factors; Uruguay; Vitamins

Endemic cancer of the esophagus has shown a positive association with the consumption of maize meal. It has been postulated that this association is due to the conversion, in the stomach mucosa, of the linoleic acid contained in maize meal to prostaglandin E2. The proportion of non-esterified linoleic acid available in the stomach may therefore be an important factor. Samples of commercially prepared maize flour, cooked and uncooked, and other maize-based foods were analysed for total and free content of various fatty acids using gas-liquid chromatography. High levels of non-esterified fatty acids (11 to 42% of contained fatty acids) were found both in maize meal and in foods prepared from it. In food prepared from maize meal, 49 mg to 363 mg non-esterified linoleic acid per 100-g sample was found. High levels of non-esterified linoleic acid in the diet, causing raised intragastric production of prostaglandin E2 and profoundly affecting the normal pH and fluid content of the esophagus, may create a predisposition to esophageal carcinogenesis.

Topics: Corn Oil; Diet; Dinoprostone; Esophageal Neoplasms; Esophagitis, Peptic; Fatty Acids, Nonesterified; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Linoleic Acid; South Africa; United States; Zea mays

Little is known about the aetiology of Barrett's oesophagus, a condition in which columnar epithelium replaces normal squamous epithelium above the juncture of the oesophagus with the stomach. An exploratory retrospective study of males from the Tucson Veteran's Affairs Medical Center (Tucson, AZ, USA), looking at 22 Barrett's cases and 22 controls, was undertaken to: (1) determine whether risk factors previously reported for squamous oesophageal cancer were also potential risk factors for Barrett's oesophagus; and (2) explore which of several retrospectively determined dietary factors would permit maximum discrimination of Barrett's cases from controls. Because of the recognized difficulty with retrospective dietary assessment, an intensive interview-based life history approach was developed to assess behavioural factors throughout adulthood. We examined the dose-response relationship involving questions (1) and (2) separately for subjects with lesions less than or greater than 7 cm in length. A literature-based oesophageal cancer risk factor score (including use of tobacco and intakes of alcohol, fat, vitamin A, linoleic acid and protein) discriminated cases from controls. Alcohol consumption alone discriminated patients with lesions < 7 cm in length from controls, and a more complex risk factor score (including tobacco use, alcohol, fat, fruits and vegetables) discriminated patients with lesions > 7 cm in length from controls.

Topics: Adult; Aged; Alcohol Drinking; Barrett Esophagus; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Fats; Dietary Proteins; Esophageal Neoplasms; Feeding Behavior; Fruit; Health Behavior; Humans; Interviews as Topic; Life Style; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Smoking; Vegetables; Vitamin A