Serum Levels of Vitamin A E B-Carotene and Folate in cases with Cervical Intraepithelial Neoplasia

Abstract

Background
A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, Tocopherols, and vitamin C with a reduced risk of certain human malignancies.

Objective
The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, vitamin A, vitamin E, B-Carotene together with Folate levels in cases with Cervical Intraepithelial Neoplasia, (CIN).

Design
Cross-Sectional Study

Setting
Al-Hussein University Hospital, El-Darassa, Cairo-Egypt.

Subjects and Methods
The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) and a control group. All women resided in the same catchment area (E-Darassa, Cairo-Egypt) and were of similar socio-economic background, representing a fairly homogenous population group. No limitation or changes were introduced in each participant’s dietary habits.

Sample of 200 women (100 women with CIN & 100 women as control) was recruited with informed consent. Plasma levels of vitamin A, vitamin E, B-Carotene and folate were measured. Results compared between cases and controls and among cases with CIN.

Results
Mean plasma level of vitamin A was significantly higher in control group than cases with CIN (P<0.001); vitamin E cases showed significantly low mean level in cases with CIN (P<0.001); mean level of B-carotene was significantly low in cases with CIN (P<0.001) and mean folate levels were significantly higher in control group than in cases with CIN (P<0.001). There were significantly lower levels of vitamin A, vitamin E, B-carotene and Folate in cases with CIN compared to control group. Levels of vitamin A and B-carotene decreases significantly with increasing CIN stage. Levels of vitamin E and folate, were insignificantly low with advanced stage of CIN.

Conclusion
The finding of a decrease in all plasma antioxidant nutrients levels, namely, vitamin A; B-Carotene and vitamin E in women with CIN suggest a potential role for antioxidant deficiency in the pathogenesis of CIN. Also Coexisting deficiency of antioxidant and folate may potentially increase the risk for CIN and consequently cancer cervix.  

Introduction
Malignancy of the lower genital tract should be considered generally preventable because of indolent growth of most tumors, the fact that most have defined biology and precursor lesions and for many of availability of active screening method such as Pap smear.

Worldwide cervical cancer is second only to breast cancer as the most common malignancy in both incidence and mortality (1).

The cervix is an ideal model for the study of chemoprevention in humans. The evidence is strong that normal cervical epithelium proceeds through a precancerous stage (cervical intraepithelial neoplasia, CIN) prior to the development of invasive cancer. In addition, the anatomical location of the cervix allows magnified visualization via colposcopy and cytological and histological samples are easily obtained in the office setting.

The evidence of a relationship between cancer and diet has received much attention in the last decade, epidemiological studies examined the relationship of cervical neoplasia with the serum level of B-carotene, alpha-tocopherol and folate. The overall evidence is only suggestive of a protective effect of these micronutrients against cervical cancer (2,3).

Recently the attention has been concentrating on the antioxidant effect of vitamins A, E and folates to protect against cancer.

Epidemiological data suggest an association between increased dietary intake of micronutrients that are high in antioxidant vitamins as vitamin A, E and C and protection against the incidence of some human cancers(4). These antioxidants appear to be essential nutritional requirements of the human female reproductive tract and are implicated in the pathophysiology and carcinogenesis of the human organs.

The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, vitamin A, vitamin E, B-carotene together with folate levels in cases with cervical intraepithelial neoplasia.

Subjects and Methods
Hundred patients with different grades of CIN were selected for this study. Another 100 women were selected from the same catchment area EL-Darassa, Cairo) with similar socioeconomic background and dietary habits with no evidence of CIN (control group).

All women were monogamy and both groups were matched for age, age at marriage, duration of marriage and parity.

All patients signed informed consent and had physical examination and pelvic examination including Pap smear and colposcopic examination with biopsies when needed.

Blood samples were collected in serum separator tubes. Collection of samples performed regardless the time of the day or the fasting state of the participant. Serum used to measure vitamin A, vitamin E, B-carotene and Folate levels.

Vitamin A and B-carotene measured by using the calorimetric assay.(5) Serum Folate levels were measured by radioassay procedure by the solid phase no boil dual count kit. Serum alpha-tocopherol levels were measured by their reduction of ferric to ferrous ions, which then form a red complex with α,? dipyridyl. Tocopherols are first extracted into xylene and the absorbance is read at 460 nm to measure the tocopherols. A correction for the tocopherols is made after adding ferric chloride and reading at 520 nm(6).

Clinical and laboratory data were recorded on an investigative report form. These data were transferred to IBM card using IBM personal computer with statistical program SPSS. Mean, standard deviation, and ranges computed with the use of unpaired t-test and chi square with significant level set at P<0.05 (CI 95%).

Results
Mean age (± SD) in cases was 40.58± 8.76 years and in controls it was 39.15±7.39 years. Mean age (±sd) at marriage was 15.84±.28  in cases and in the control group it was 17.10±2.28 years. The mean duration of marriage in cases (±sd) was 24.29 ±8.52 years and in control group it was 22.11±6.7 years. Mean number of pregnancies in cases was 5.95±1.59 pregnancies and in the control group it was 5.95±1.11 pregnancies.

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