Oesophageal Cancer Research Unit

Current projects

The role of dietary fatty acids in cancer prevention
Both epidemiological studies in humans and animal experimental studies have shown that focal cell proliferation - e.g. papillomas in oesophageal cancer - are the critical early lesions for the development of cancer.

The studies have also shown that tumour development can be affected by the type and quantity of dietary fat intake. Diets high in the n-6 fatty acids, especially linoleic acid (LA; C18: 2n-6), have led to increases in the size, number and occurrence of tumours. On the other hand, the n-3 fatty acids led to a decrease in the size and number of tumours, as well as an increase in the latency period of tumour occurrence.

Human papilloma virus types associated with oesophageal cancer
The most remarkable feature about oesophageal cancer (OC) is its geographic and ethnic variations in incidence. The areas in the world with a high incidence of OC include the Transkei in South Africa, the shores of the Caspian Sea in northern Iran, the Henan and Shanxi provinces of China, South America and the southern areas of France.

High risk factors leading to the onset of OC include smoking, drinking and nutritional deficiencies.

In developed countries, the most commonly mentioned risk factors are high alcohol intake and cigarette smoking, especially when combined. In developing countries, nutritional deficiencies, chewing and smoking habits (betel, tobacco, opium), and exposure to nitrosamines are also of major importance.

In 1982, human papilloma virus (HPV) was linked for the first time with the development of OC. In humans, over 73 papilloma virus types have been identified on the basis of sequence homology. The association of certain types primarily with normal tissue and benign lesions, as opposed to other cancer associated types, has led to the concept of low and high oncogenic risk HPV's respectively.

In high risk regions world-wide, such as the Transkei, HPV infection has been found in a high proportion of oesophageal cancers. Studies carried out on different population groups in both high and low risk geographic areas have reported conflicting results, with prevalence rates ranging from 0% to 71%. The differences in the data could be due to variations in specificity, sensitivity and feasibility in analytical techniques used.

Compared with other laboratory techniques, the polymerase chain reaction (PCR) is a simple, rapid, sensitive method for detecting human papilloma virus DNA in samples. Furthermore, the use of consensus primers is an advantage in PCR based studies as these primers can detect a wide spectrum of HPV, including novel types.

Both of these detection techniques will be used in the above project in order to determine more accurately the association between OC and HPV in the Transkei.

Antimutagenic, antiproliferative and cancer modulating properties of SA herbal teas
Oesophageal cancer is the most common cancer among South African black males (age standardised incidence rate - ASIR = 24.9/100 000), while liver and colon cancer rates fall within the top ten cancers prevalent in all race groups (Sitas, 1992).

Colon cancer is steadily increasing in all populations due to changes towards a more Western type diet. The cancer modulating effects of green and black tea extracts on mouse skin, colon, lung and rat oesophageal cancer have been reported previously (Yang and Wang, 1993).

Very little is known about the modulating effect of Southern African herbal teas ("Rooibos", honey bush) and Magwa teas on any type of cancers, although research conducted by Shimoi (1994) and Sasaki (1993) suggests that they may contain more potent antimutagens than green and black teas.

Evaluation of the antimutagenic and anticarcinogenic properties of these South African teas will play a valuable role in determining their possible use in cancer prevention.

This project will study the possible chemo-preventative and/or cancer modulating effects of South African herbal teas and Magwa tea on the development of oesophageal cancer.

Genetic mutation and genes involved in tumour metastasis
Tumour cell invasion and metastasis is the most devastating aspect of cancer. As long as the cancer is localised to a specific site, surgical resection remains a viable option. As soon as the primary tumour has metastarised to other sites, treatment is no longer possible.

Examination of the molecular events leading to tumour metastasis is crucial since an understanding of these events may make it possible to design specific inhibitors to block metastasis.

Mutations in several tumour suppressor genes and oncogenes have been shown to influence connective tissue synthesis and deposition in tissues. Decreased connective tissue deposition and increased degradation is an important prerequisite for tumour invasion and metastasis.

Recent studies have shown that mutant oncogenes and tumour suppressor genes are capable of modulating the expression of connective tissue proteins such as collagen. The studies showed that tumour cells are able to down-regulate collagen production in adjacent normal fibroblasts.

The above study investigated whether there is a possible link between oncogene or tumour suppressor gene mutations and metastatic potential.

Genetic polymorphisms in drug metabolising genes
The development of cancer has in many instances been linked to exposure to genotoxic compounds that can induce DNA damage. Drug metabolising enzymes such as the cytochrome p450, the glutathione-s-transferases and the n-acetyltransferases are involved in detoxification of these toxic compounds. It has been shown that certain genetic variants of these genes have different activities that may result in the accumulation of highly reactive metabolites of these toxins in different tissues.

In this study we will investigate the occurrence of the various genetic polymorphisms of the above genes in OC patients and in normal control individuals in South Africa.

Research for candidate genes in oesophageal cancer
Oncogenic transformation of normal cells into tumour cells is accompanied by the altered expression of a large number of genes. The expression of some genes may be elevated, while the expression of others may be decreased or even totally abolished. In this study differential display reverse transcriptase PCR (PRT-PCR) was used to identify differentially expressed genes in oesophageal cancer.

The role of these differentially expressed genes in carcinogenesis is currently been investigated.