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Indian Journal of Cancer
Medknow Publications on behalf of Indian Cancer Society
ISSN: 0019-509X EISSN: 1998-4774
Vol. 40, Num. 2, 2003, pp. 67-70
Untitled Document

Indian Journal of Cancer, Vol. 40, No. 2, (April - June 2003) , pp. 67-70

Association of Vitamin A, Vitamin C and Zinc with Laryngeal Cancer

Kapil U, Singh P, Bahadur S,* Shukla NK,** Dwivedi S,*** Pathak P, Singh R***

Departments of Human Nutrition, *Otorhinolaryngology, **Surgical Oncology and ***Biostatistics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029. India.
Correspondence to: Umesh Kapil. E-mail: kapilumesh@hotmail.com

Code Number: cn03010

ABSTRACT

BACKGROUND: The incidence of the cancers of the oral cavity, pharynx, esophagus and larynx in different population groups of India is amongst the highest reported in Asian countries. There is evidence that high dietary carotenoids and vitamin C may possibly decrease the risk of laryngeal cancer. Limited data is available from India on the association between these micronutrients and the risk of laryngeal cancer. AIMS: To assess the levels of vitamin A, vitamin C and zinc in laryngeal cancer patients and healthy controls. SETTING AND DESIGN: A hospital based case- control study. MATERIAL AND METHODS: One hundred and fifty five laryngeal cancer patients and a control group of 155 healthy individuals constituted the study population. Individuals in the control group were individually matched with the patients for their age ± 2 years, sex and place of residence. Venous blood was drawn from the cases and controls and estimations of vitamin A, zinc and vitamin C was done utilizing the standard procedures. STATISTICAL ANALYSIS USED: Paired `t' test to compare the mean serum levels of vitamin A and zinc and plasma vitamin C between laryngeal cancer patients and controls. Univariate logistic regression analysis to calculate the odds ratios and the confidence intervals. RESULTS: The mean serum vitamin A, zinc and plasma vitamin C levels were significantly lower in laryngeal cancer patients as compared to the controls. CONCLUSIONS: The findings of the present study indicated a strong association of these micronutrients with laryngeal cancer in the Indian population.

Key Words : Laryngeal cancer, Micronutrients, Status, Diet.

Introduction

During the recent years the importance of nutrients in the etiology of many cancers has gained wide acceptance. Diet containing anticarcinogenic substances such as carotenoids, vitamin C and trace elements have been documented to have a role in the prevention of the carcinogenic process in experimental and animal model studies.1

Cancer of the larynx is the fourteenth most common cancer in the world.2 The incidence of the cancers of the oral cavity, pharynx, esophagus and larynx in different population groups of India is amongst the highest reported in Asian countries.3 There is evidence that high dietary carotenoids and vitamin C may possibly decrease the risk of laryngeal cancer.4 Limited data is available from India on the association between these micronutrients and the risk of laryngeal cancer. We conducted a hospital based case- control study to examine the association of vitamin A, vitamin C and zinc with laryngeal cancer. The results of the present study can be used for further identifying research issues on the role of nutritional factors in laryngeal cancer in the Indian context.

Material and Methods

The present study was a hospital based case _ control study. One hundred and fifty five incident laryngeal cancer patients from the out patients and hospital admissions of the department of Otorhinolaryngology and head and neck tumor clinic at the Institute Rotary cancer hospital at All India Institute of Medical Sciences, constituted the study population. The mean duration of appearance of symptoms for laryngeal cancer was 6 months. The criteria for the selection of patients were i) proven cases of laryngeal cancer by biopsy and histopathology; ii) who had not undergone any treatment ie. chemotherapy or radiotherapy;

iii) who were in good mental health to give reliable answers to the questionnaire; iv) who did not suffer from any major illness in the past, before the diagnosis of laryngeal cancer so as to change their dietary consumption pattern; v) who had not taken long course of any vitamin or mineral supplement during the last one year and vi) who were not on corticosteroid therapy or were not suffering from hepatic disorders or severe malnutrition. The participation rate amongst the cases was 100%.

One hundred and fifty five healthy individuals not suffering from any major illness attending the out patients of the department of Gastroenterology at All India Institute of Medical Sciences constituted the control group. The criteria for the selection of controls was i) who were not related to the patients included in the study ii) who were not suffering from any cancerous lesions iii) who were in good mental health to give reliable answers to the questionnaire; iv) who had not taken long course of any vitamin or mineral supplement during the last one year. Individuals in the control group were individually matched with the patients for their age ± 2 years, sex and place of residence. The participation rate amongst controls was 80%. An ethical clearance was obtained from the local review board of the institute and the informed consent of the patents and controls to participate in the study was taken. The patients and the controls were subjected to similar investigations.

Venous blood from antecubital vein was drawn from the cases and controls and was collected in i) heparin coated and ii) uncoated amber coloured polypropylene tubes for separation of plasma and serum, respectively. The tubes were flushed with nitrogen for 30-60 seconds and tightly capped prior to blood collection. The tubes were placed in an ice box and transported for centrifugation. The samples were centrifuged at 3500 rpm at 40C for 30 minutes for the collection of sera and plasma. Sera and plasma was collected in 0.5ml ependroff vials which were labelled previously and stored at -700 C until analysis. Estimation of vitamin A, zinc and vitamin C was done utilizing the standard procedures.5-7

On account of the matched case- control design used in the study, paired `t' test was used to compare the mean serum levels of vitamin A and zinc and plasma vitamin C between laryngeal cancer patients and controls. The result was considered significant at 5% level of significance. The univariate logistic regression analysis was also carried out to calculate the odds ratios and the confidence intervals.

Results

A total of 155 laryngeal cancer patients and controls were included in the present study. Nearly 89% of the subjects were males and majority of them were in the age group of 41-60 years (52.8%). Table 1 depicts the mean serum vitamin A, zinc and plasma vitamin C levels of laryngeal cancer patients and controls. The mean serum vitamin A levels were significantly lower (36.43 ± 23.09) in laryngeal cancer patients as compared to the controls (53.51 ± 37.76). There was a statistically significant difference in the mean vitamin C and zinc levels in the laryngeal cancer patients and controls.

There was a 2% and 1% lower risk of laryngeal cancer if the levels of vitamin A and zinc were increased by 1 unit, respectively. The odds ratio for vitamin C was 0.58 resulting in a 42% lower risk of laryngeal cancer if the level was increased by 1 unit.

Discussion

The findings of the present study indicated a strong association of vitamin A with laryngeal cancer. The cases had significantly lower serum levels of vitamin A as compared to the controls. An earlier study conducted in Poland revealed similar results in which the laryngeal cancer patients had significantly lower vitamin A concentrations as compared to the control subjects of similar age.8 Two case control studies have also reported a statistically significant odds ratio of 0.5 for high intake of carotenoids.9,10 Vitamin A plays an important role in cell differentiation and lack of cell differentiation is an important feature of cancer cells. Precursors of vitamin A (retinoids) have been categorised as potential chemo-preventive agents that act both as suppressing agents which retards the development of neoplasia in cells and as inhibitors of tumor promotion. The anti-cancer role of carotenoids is related to their ability to quench singlet oxygen. Beta-carotene deactivates excited oxygen molecules that are generated as by-products of normal metabolic processes and traps free radicals. These antioxidant effects may protect cells against oxidative DNA damage.11,12

There was a strong association of serum zinc levels with laryngeal cancer in the present study. A study conducted in 1993 amongst laryngeal cancer patients found that the dietary intake of zinc was inversely related to the risk of laryngeal cancer. However, they found no difference between cases and controls in the concentrations of zinc in nail tissues.13 Zinc is mainly required for DNA synthesis, cell division, and protein synthesis. Zinc directly stimulates DNA synthesis by altering the binding of F and F3 histones to DNA so as to affect RNA synthesis. It has been hypothesised that zinc could be operating at several different levels and influencing lymphocyte monoclonal proliferation.14 The lower levels of vitamin A in laryngeal cancer patients have been found to be significantly correlated with serum concentrations of zinc and retinol-binding protein (RBP). It has been suggested that lower levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver stores.15

In our study we also found an association of vitamin C with laryngeal cancer. An earlier multi- centric case control study found that the people with the highest level of vitamin C intake were at a low risk for laryngeal cancer as compared to people in the lowest quintile.16 The mechanism of anticarcinogenic role of vitamin C lies in the fact that it prevents the formation of carcinogens from precursor compounds.17 It may prevent cancer through its ability to scavenge and reduce nitrate, thereby reducing the substrate for the reaction with secondary amines to form nitrosamines. Also, vitamin C is an antioxidant and plays a protective role in the immune system. It also plays an important role in the hydroxylation of lysine and proline, in the synthesis of connective tissue proteins, such as collagen. A deficiency of vitamin C may, therefore, affect the integrity of intercellular matrices and thus may promote tumor growth or inhibit tumor encapsulation.18 The main objective of the present study was to assess the levels of vitamin A, vitamin C and zinc in laryngeal cancer patients and healthy controls. Smoking and alcohol intake are the major risk factors for laryngeal cancer. It is known that both these factors are associated with plasma vitamin C and serum carotene levels. In the present study we did not collect data on these confounding variables and this is one of the potential limitations of the study.

Nutrient deficiencies in developing countries can be a significant contributing factor in modifying the multistage process of carcinogenesis. The epidemiological evidence is sparse and we are convinced that the field is much more complex than it appears at this early stage of enquiry. The relationship between dietary constituents and cancer is complex and it is not easy to quantify the contribution of diet to cancer risk. The consistent observations across wide population groups in different countries strongly support that vitamin A, vitamin C and zinc are important chemopreventive agents.19,20 Our data does not allow us to conclude whether vitamin A, vitamin C and zinc deficiency preceded or occurred as a result of the cancer. However, the low mean serum vitamin A and zinc and plasma vitamin C levels in laryngeal cancer patients as compared to the controls indicated there strong association with laryngeal cancer in the Indian population.

Acknowledgements

We would like to thank Division of Non- Communicable disease, Indian Council of Medical Research, New Delhi for providing us the financial grant vide their letter No. 5/8/10-1(Oto)/98-NCD-I for conducting the study.

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Copyright 2003 - Indian Journal of Cancer


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