Study of mineral changes in patients with upper gastrointestinal cancer

Abstract              Background: Cancer has emerged as a major public health problem in developing countries, matching its effect in industrialized nations. It is a leading cause of death worldwide. In India, oesophagus and stomach cancers are reported to have higher incidence. Material and Methods: This comparative study carried out in patients suffering from oesophagus and stomach cancer and healthy subjects at KEM and Tata hospital, Mumbai. Sixty healthy and sixty cancer patients were enrolled in this study after confirming their eligibility based on inclusion criteria. The serum levels of calcium, phosphorus, zinc, copper and magnesium were measured. The data collected was statistically analysed and evaluated for correlation between parameters and type of cancer. Results: In both oesophagus and stomach cancer patients, serum calcium and serum phosphorus levels showed elevation in comparison to control group. Serum zinc and copper levels also remained elevated in oesophagus and stomach cancer patients but serum magnesium showed decrease levels in both cancer patients. Positive correlation studied between calcium/phosphorus, calcium/magnesium and copper/zinc ratios in both groups of cancer patients. Conclusion: Based on the data, association of selected minerals studied with oesophagus and stomach cancer patients can be observed. A well planned and extensive large sample study will be required to assess the therapeutic potential of minerals in decreasing the cancer risk.

Key Words: minerals, calcium, zinc, copper, phosphorus, magnesium, cancer, oesophagus, stomach.

INTRODUCTION

The origin of the word cancer is credited to the Greek physician Hippocrates who used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab. The Roman physician, Celsus, later translated the Greek term into cancer, the Latin word for crab. Nowadays Cancer, among various diseases has become a big threat to human beings globally. This is the second most common disease after cardiovascular disorders for maximum deaths in the world. deaths in the world This is the second most common disease after cardiovascular disorders for maximum deaths in the world In spite of good advancements for diagnosis and treatment, cancer is still a big threat to our society (Kotnis et al, 2005). This is the second most common disease after cardiovascular disorders for maximum deaths in the world (Jemal et al, 2007). It accounts for about 23 and 7% deaths in USA and India, respectively. The world’s population is expected to be 7.5 billion by 2020 and approximations predict that about 15.0 million new cancer cases will be diagnosed; with deaths of about 12.0 million cancer patients (Brayand et al, 2006). The prevalence of cancer in India is estimated to be around 2.5 million, with about 8, 00,000 new cases and 5, 50,000 deaths per annum (Nandakumar, 1990-96). According to 1991 Indian census data, about 609000 cancer cases have been observed. This number had drastically increased to 806,000 by the end of the last century; with 96.4 and 88.2% age standardized rates for males and females; out of 100,000 cases analyzed (Rao et al, 1998). During last one decade, about 70% cancer cases have been diagnosed and treated with survival of a few patients (Dinshaw et al, 1999). It is believed that in near future the number of cancer patients will increase in the developing and under developed countries, which may rise up to 70%; a serious issue for all of us. The magnitude of cancer problem in the Indian Sub-continent (sheer numbers) is increasing due to poor to moderate living standards (Wynder et al, 1974) and inadequate medical facilities. Most frequently observed cancers in Indian population are of lungs, breast, colon, rectum, stomach and liver (Nandakumar, 1990-96; Rao et al, 1998; Murthy et al, 2004). Nowadays, India is growing with a good progress rate and probably will become a developed country within a few decades resulting into its participation in the world development. Therefore, it is important to study the status of cancers in India so that advance measures may be taken to control this havoc in near future. In view of these facts, attempts have been made to study the status of cancers in India including its causes, preventive measures, effect on Indian economy and comparison with global scenarioThe prevalence of cancer in India is estimated to be around 2.5 million, with about 8, 00,000 new cases and 5, 50,000 deaths per annum¹. The magnitude of cancer problem in the Indian Sub-continent is increasing due to poor to moderate living standards ² and inadequate medical facilities. Most frequently observed cancers in Indian population are of lungs, breast, colon, rectum, stomach and liver^3,4. The causes of such high incidence rates of these cancers may be both internal (genetic, mutations, hormonal, poor immune conditions) and external or environmental factors (food habits, industrialization, over growth of population, social etc.). Most of the cancers have some relationships with diet. Predominant among them are cancers of the oesophagus, stomach, colon and liver. Carcinomas of the oesophagus are closely related to smoking and to the consumption of alcohol. With the absence of either of the risk is reduced by three quarters, the risk is reduced only very little more by the absence of both, as the two factors interact synergically. Nutritional deficiencies have probably also played a part particularly in the women. High rate of incidence is seen in China and India. Cancers of oesophagus recorded for 10% of all cancers in males and 5% in females.⁵ Gastric cancer is the fifth most common cancer among males and seventh most common cancer among females in India.³ The aggressiveness of the disease and need for improvement in therapeutic options is discerned by the fact the gastric cancer is the second most common cause of cancer death globally.⁶Trace elements are the micronutrients that are part of daily diets and are required in minute quantity. These elements are very important in many different biological processes, such as normal healing, metabolism of genetic materials for growth and differentiation, function of structural nutrients, even in programmed cell death and necrosis. This helps in protection against oxidative injuries. These also possess anti-inflammatory and anti-carcinogenesis effect. But some elements are also involved in causation of undesirable events in vivo, such as participation in carcinogenesis and sustenance of cancerous cells. Role of lead, copper; chromium and zinc have been implicated in this effect. The in vivo utilization of trace elements is complex and not completely understood. They have redundancy of function because the same element may incite both positive and negative events depending upon its concentration and interaction with other trace elements.⁷There are numerous influencing factors which decide the concentration of trace elements in body fluids and tissues, like sex and age, the dietary intake, uptake in the gastrointestinal tract, storage, excretion and the presence or absence of disease state. Studies have been undertaken to identify the appropriate tissue for estimating the bioactivity of these elements. However, for some of these elements like zinc, copper and selenium etc, the serum concentration has been found to be is a reliable measure of their bioactivity in the body^{, 8}Stomach cancer is the second-most common cancer among men and third-most among females in Asia and worldwide. The symptoms and sign of the stomach cancer are often reported late when the disease is already in advanced stages and 5-year survival is less than 30% in developed countries and around 20% in developing countries.⁹ In India, the number of new stomach cancer cases in 2001 was estimated to be approximately 35,675 (n=23,785 in men; 11,890 in women).¹⁰ These differences in incidence rates can be attributed to many factors but refer particularly to differences in dietary habits, and infection to Helicobacter pylori. Esophageal cancer (EC) is the eighth most common cancer worldwide with a case fatality rate of 90%. It is one of the malignancies with highest geographic, ethnic, and gender variations. In India, in states such as Karnataka, Tamil Nadu, Kerala, and Assam, EC is the most common gastrointestinal (GI) malignancy.¹¹Due to the inconsistencies in the documentations on trace elements and some minerals in cancer of the Oesophagus and stomach, the present study was planned to compare the serum concentration of major minerals and trace elements in serum of patients afflicted with oesophagus and stomach cancer and also study gender wise effect in these study groups in comparison to healthy controls.

MATERIALS AND METHODS

The present study was carried out in department of biochemistry of Seth GS Medical College and KEM Hospital, Mumbai and Tata Memorial Hospital, Mumbai after obtaining the sanction of the hospital ethics committee. Patients suffering from cancer were considered after confirming on inclusion criteria, referred either from Tata or KEM Hospital. In this study, 30 patients each in 2 groups suffering from oesophagus and stomach cancer along with 60 normal healthy in control group were evaluated. The study was carried out on newly diagnosed cancer patients and grouped them as given below;

All these patients along with normal healthy controls were evaluated first clinically and then laboratory investigations like serum calcium, serum phosphorus, serum zinc, serum copper and serum magnesium were carried out. Blood samples collected by venepuncture, were allowed to clot at room temperature and serum was separated within 2 hours of withdrawal of blood and divided into aliquots which were stored at 4⁰C until analysed. Spectronic 20 Spectrophotometer, Shimadzu’s UV- Spectrophotometer, Remi’s refrigerated centrifuge, ordinary centrifuge and vortex mixture were used for estimation. The data collected from the analysis of serum were statistically analysed and evaluated for association between parameters and type of cancer.

Male patients in Oesophagus cancer group showed statistically significant increase in the calcium/magnesium ratio and decrease copper/zinc ratio whereas female patients in Oesophagus cancer group showed increase in calcium/magnesium ratio and decrease in the copper/zinc ratio. In case of male patients in stomach cancer group, data reveals only the statistically increase in calcium/magnesium ratio. Female patients in stomach cancer group showed percentage increase in the ratio of calcium/magnesium ratio which is statistically significant.

DISCUSSION

The biologic and pathologic role of minerals and trace elements are numerous, complex and their role apparently depends on the concentration and the balance of the positively and negatively implicated elements among other factors. Sometimes balance may lead to inconsistency. Due to multiplicity of function and the varying role depending on balance and concentration, the role of these elements is yet not fully elucidated. Zinc, most researched mineral, is an essential constituent of more than 100 enzymes and is essential for life. Through its function in nucleic acid polymerases, zinc plays a predominant role in nucleic acid metabolism, cell replication, tissue repair, and growth.¹² Some epidemiological studies have suggested that higher levels of dietary zinc are associated with an increase in the incidence of cancer at several different sites, including the breast and stomach, and other studies have reported lower levels of zinc in the serum and tissue of patients with esophageal, bronchogenic, and other cancers, compared to corresponding levels in controls.¹³ In our study serum zinc levels in both gender showed increase in oesophagus and stomach cancer patients. The possibility that dietary exposure to copper, through the copper content of either foods or cookware, may play an etiologic role in gastric carcinogenesis is raised by the experiments of Endo et al ¹⁴, who found that the copper ion may be involved in conversion of creatine and creatinine to methylguanidine, a precursor of methylnitrosoguanidine. However, no epidemiological data on the relationship of gastric cancer and dietary copper have been reported. Magnesium deficiency may result in a variety of metabolic abnormalities and clinical consequences even cancer development.¹⁵ In our study reported increase in serum copper levels and decrease in serum magnesium levels in oesophagus and stomach cancer patientsThe association of serum trace elements and high cancer risk has been found in many studies.^16,17,18,19 Sullivan F.et al.²⁰ found that serum selenium and zinc levels were low while copper level were high in various human cancers in west Virginia. Mark et al.¹⁶ found that human squamous cell carcinoma esophagus patients had a significant low level of serum zinc as compared with age matched healthy controls (P<0.01). Umesh Kapil et al.²¹ observed that 53% of study people (Jharkand) had serum zinc deficiency and the deficiency was higher in females as compared to males. Limited data are available in India to show the association of cancer esophagus with serum level of trace elements (Zn, Copper, Selenium). The scientific community is convinced that both genetic and environmental factors play important role in oesophageal carcinogenesis. Although, inherited high susceptibility to oesophageal cancer accounts for part proportion of cases, exogenous exposures are also important for causing this disease. A number of studies have suggested that dietary factors are significant to the development of EC^22,.23,.24 and there is evidence that different varieties of food and nutrients could play a role in protecting against this disease.^25,26 A study conducted by Chen et al²⁷ in china concluded that zinc and copper intake was inversely related to oesophageal cancer mortality and calcium intake level was positively related to oesophageal cancer mortality. Despite poor survival rates and a relatively high incidence in certain regions of the world, the impacts of mineral intake on the etiology of ESCC are unknown. Exposure to trace metals and tissue concentration of trace element is a modifiable risk factor. Hence, discovery of a credible and strong causal association between trace elements and cancer of the oesophagus and stomach may create a new frontier for the prevention and management of an established disease.

CONCLUSION

About the role of mineral intake in the development of oesophagus and stomach cancer, limited data is available. In this study, we tried to investigate a possible link of dietary calcium, phosphorus, copper, zinc and magnesium intake with oesophagus and stomach cancer risk. A well planned and extensive research will help in identifying therapeutic potential of use of minerals in these types of cancer patients.

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