Association between Vitamin D deficiency and Breast Cancer

Objective: To determine the association between vitamin D deficiency and breast cancer. Methods: This case control study included 94 female patients aged 20-75 years of any marital status and parity. Newly diagnosed 42 breast cancer patients who presented to surgical OPD of Dow University Hospital from Jan 2016 to June 2016 were included into the study as “cases” after informed consent. Age-matched 52 females who presented to OPD for complain other than breast pathology were included as the “control group”. The sociodemographic of both cases and controls and histopathological characteristics of cases were recorded. Serum 25-(OH)2D levels were studied by the ELISA technique and recorded in ng/ml. Vitamin D deficiency was considered at serum level less than 20 ng/ml. Results: Mean age was 40.1 Years for controls and 47.6 Years for cases. Mean height, weight and BMI did not differ between cases and controls. Serum Vitamin D levels were significantly lower in cases (85.7%) than controls (55.8%). The unadjusted and adjusted ORs for breast cancer in cases and controls showed a statistically significantly increased risk of breast cancer with low vitamin D concentration (p value0.003). After adjustment for age, parity, BMI, sun exposure, economic status and education status the ORs (95% CIs) for breast cancer risk was7.8 (1.99 - 30.58) for women with vitamin D concentrations <20 ng/mL. Conclusion: Findings of our study conclude that vitamin D deficiency is associated with risk of breast cancer.


INTRODUCTION
Breast cancer poses a serious health risk for women throughout the world. It is the most common cancer among women in United States. 1 It accounts for 22% of all female cancers worldwide and approximately 42% cases occur in developing countries. 2 Breast cancer is also the commonest cancer of females in Southern and Northern Pakistan. 2 For the large magnitude of breast cancer, a lot of efforts are being made to identify such risk factors that can be modified to prevent breast cancer. Vitamin D is assumed to be one of such risk factors. It is a fat soluble vitamin. Its main sources are skin production (via exposure to ultraviolet light) and dietary intake. Vitamin D has an important role in calcium and bone homeostasis. Vitamin D has

Original Article
Association between Vitamin D deficiency and Breast Cancer not only shown to strengthen our bones but it also has capability to modulate several features of cancer. Its anticarcinogenic properties include inhibition of cell proliferation, invasion, metastasis and angiogenesis and induction of apoptosis and differentiation. 3 In a study done in Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan vitamin D deficiency was found in 95.6% of breast cancer patients and in 77% of control group. 4 Several studies have been done to evaluate the association of vitamin D deficiency and breast cancer risk. There is controversy in the literature about this association. Some studies have found that breast cancer is associated with low levels of vitamin D. [5][6][7][8][9] However there is a study published in 2007 that showed no association between breast cancer risk and vitamin D levels. 10 Low vitamin D levels is frequently found in our population. 11 If we can establish an association between the two in our population we will be able to give recommendations to take corrective actions and try to reduce the incidence of breast cancer in our population.

METHODS
This case control study was approved by the College of Physicians and Surgeons Pakistan. Sample size was calculated by using WHO sample size calculator with 80% power of test and 5% level of significance considering proportions (P1=95.6%) 4 and(P2=77%) 4 in case and control groups to be atleast 42 patients in each group. Newly diagnosed 42 breast cancer patients who presented to the OPD of surgical department of Dow University Hospital were included into the study as "cases" after informed consent over a period of 6 months from Jan 2016 to June 2016. Age-matched 52 females who presented to OPD for complain other than breast pathology were recruited as the "control group." Patients were recruited according to nonprobability consecutive, meeting inclusion and exclusion criteria. were recorded by direct questioning on to the proforma for the whole study population. The histopathological diagnosis of breast cancer, grade, stage of the tumor, and hormone receptor status (estrogen receptor -ER, progesterone receptor-PR, and Her2neu) was recorded from the pathology reports of breast cancer patients. Serum 25-(OH)2D levels were studied by the ELISA technique on the blood samples drawn of the study population at their initial presentation and the values were recorded in ng/ml. Vitamin D deficiency was considered at serum level less than 20 ng/ml. Statistical Analysis: Data was analyzed by using SPSS version 20 on computer. Categorical variables in cases and controls like marital status, parity, grades, stages, histopathology, receptor status of tumor, exposure to sunlight, economic status, education status and vitamin D deficiency were presented in frequency and percentages. Mean+/-SD was computed for numerical variables like age, size of tumor, duration of carcinoma breast,

RESULTS
Data of 94 women, including 42 breast cancer cases and 52 controls, were included in analysis. The characteristics of study population are shown in Table-I and II. Mean age was 43.47 years, mean height was 1.54 meters, mean weight 68.01 kilograms, mean BMI 28.83 kg/m 2 , mean duration was 6.14 months and mean size of breast cancer was 3.82 centimeters. Mean age was 40.1 year for controls and 47.6 year for cases. Mean height, weight and BMI did not differ between cases and controls.
Serum Vitamin D levels were significantly lowers in cases than controls. 85.7% of cases and 55.8% of controls had Vitamin D levels less than 20 ng/ ml. Only 14.3% of cases and 44.2% of controls had Vitamin D levels above 20 ng/ml (Table-III).
The ORs for breast cancer in cases and controls by category of vitamin D status are shown in Table-    ml) in 28% of controls and 33% of cases. 1 Many observational and crossectional studies reflect that deficiency of vitamin D is commonly found in patients with breast cancer. 12,13 Some studies have also demonstrated a protective effect of vitamin D on breast cancer risk. 14 Several studies have shown a negative relationship between sunlight exposure and breast cancer risk. Proposed mechanism for this negative association is sunlight induced dermal synthesis of vitamin D, which evidence suggests, can reduce the risk of breast cancer. 15 In our study, parity, BMI, sun exposure, economic status and education status did not show any statistically significant association with breast cancer risk. In our study 71.4% of cases and 46.2% of controls were overweight that may link increased frequency of vitamin D deficiency in cases as compared to controls because of high BMI as shown in study of Imtiaz et al. 4 The topic of vitamin D deficiency and breast cancer risk is a field of intense study and many aspects of it require further investigations.
Conclusion: Findings of this study show that vitamin D deficiency is associated with risk of breast cancer.