The Associations Between Vitamin D and Breast Cancer
According to the Center for Disease Control and Prevention (CDC), around 220,000 women are diagnosed with breast cancer each year in the United States.1 Breast cancer is a disease in which malignant cells form in the tissues of a woman’s breast.2 Breast cancer is among the most commonly diagnosed cancer, making it the second leading cause of death in women in the United States.1 Out of the 220,000 women diagnosed, around 40,860 of them die each year. Although there is not a cure for cancer, new research findings suggest associations between vitamin D (VD) and a decrease risk of diseases, such as cancer. Early epidemiological studies of cancer cells in mice has found that VD has several factors that might slow or prevent the development of cancer.3 Such activities include promoting cellular differentiation, decreasing cancer cell growth, stimulating apoptosis, and reducing tumor blood vessel formation. Because early epidemiological research showed that death rates for certain cancers was lower among individuals living in southern locations than those in northern ones, it was hypothesized that ultraviolet exposure from the sun, which leads to the production of vitamin D, might account for this association.3 Researchers wanted to further analyze the research gaps of these finding with vitamin D, but this time in relation to women and potential risk of breast cancer.
Vitamin D, a fat-soluble vitamin, can be synthesized by the body through ultraviolet light exposure and dietary sources.4 Previous research has suggested vitamin D containing an anti-inflammatory effect that could interfere with cancer cell pathways. Some countries, such as countries in northern Europe, have limited sunlight, which make it difficult to maintain an optimal vitamin D level through diet alone.4 A study conducted in Istanbul, Turkey, sought to determine the prevalence of VD deficiency as measured by serum 25-OH D (25-hydroxy vitamin D level blood test) levels in patients with breast cancer. To evaluate its correlations with life-style and treatment, 25-OH D was defined as the sufficient level that would be measured throughout the study and VD deficiency was ranged <10 ng>25, no bisphosphonate usage, and a conservative dress code with 70% of participants being insufficient.4 Although the data collected suggests a relationship between dress code and supplementation with VD deficiency, there are some limitations to this study. Researchers did not take into account dietary intake of VD, which could have also played a role in VD levels in patients who were taking high dosages of supplements. Like any study, limitations such as this variable could have influenced the data during the time it was being analyzed.
Similar to the previous study, this one also measured VD supplementation in women. However, this study also took into consideration the dietary VD intake of participants.5 Despite the widespread fortification of VD in foods in the U.S, approximately 42% of women have inadequate levels of VD, <25 OHD.3 The Sister Study recruited 50,884 women who had never had the disease, but who had a family history of breast cancer. Variables that could influence VD intake, such as portion size of VD containing foods, menopausal status, vitamins, BMI, and time spent outdoors were assessed throughout the five-year period of the study for all participants. Data on potential risk factors and current health status were collected through telephone interviews and self-completed questionnaires. Female examiners also visited the participants’ homes throughout the study to collect blood samples. Researchers selected 3,392 participants for a VD sub study, 1,616 of them being breast cancer cases and 1,844 randomly sampled from the Sister Study cohort. Different models with 25-OHD samples collected from the participants were used in the study for each of the different variables. The samples collected were adjusted to fit the variables measured at baseline. At the end of the study, cases more prone to get breast cancer were women who were older, nonwhite, highly educated, postmenopausal with high BMI, as well as having had a prior relative diagnosed with the disease. The participants that took vitamin D supplementation on a daily were found to have a 21% lower risk of breast cancer. The overall conclusion of this study was that there could be an associated with a reduced risk of breast cancer for women who increase VD supplementation. Studying sisters could potentially increase the understanding of the interplay of genes and environmental factors in breast cancer to identify methods to approach this disease.5 As all studies, this one also included some limitations such as self-reported dietary VD intake, supplement use, and time spent outdoors. These factors could have biased the overall data if participants did not calculate the variables correctly, thus influencing the results of the study, and making it difficult to provide public recommendations on how to modify VD intake levels.
Past studies conducted in Pakistan found that breast cancer is associated with low levels of VD.6 However, one study published in 2007 showed that there was no associated between these two. Therefore, researchers at Dow University wanted to further study these two associations. Ninety-four patients were studied that appeared at the university, 42 of them being breast cancer patients, serving as cases, and 52 of them having no pain relation to breast pathology serving as the control group. Deficiency of VD was calculated as a number below 20 ng/ml. Sociodemographic and histopathological factors were calculated for six months from each patient. Sociodemographic factors were calculated by direct questioning and histopathological factors, such as hormone receptor status were calculated from the pathology reports of breast cancer patients. Serum 25-OHD levels were measured each time patients appeared at the university and plotted into logistic regression models to assess associations between VD deficiency and breast cancer. After six months, data demonstrated serum VD levels were significantly lower in cases than those in controls. Eighty-six percent of cases and 55.8% of controls had VD deficiency. After categorical variables were assessed, such as age, BMI, sun exposure, economic and educational status, breast cancer prevalence was doubled for women with VD concentrations already below 20ng/mk. However, there was no significant association with breast cancer risk if the categorical variables were measured alone without VD calculations.6 Although the data correlated with the hypothesis of the study, the duration of the study was a limitation. The data could not be considered as reasonable that deficiency in VD is associated with an increased risk of breast cancer because a higher number of participants as well as a longer duration time of study is needed.
Another study was conducted in the Comprehensive Center in Montpellier and at the University of Iowa Holden Comprehensive Cancer to determine whether a larger population deficient in VD was more prevalent to breast cancer than in a population who had a higher vitamin D level.7 In this study, not achieving a pathological complete response (pCR), lacking all signs of cancer in tissue samples removed, was associated with a deficiency in VD, <20ng>
Because there are research gaps between VD and breast cancer, researchers in Maryland took another approach, this time looking at vitamin D and DNA methylation. Past studies have determined that vitamin D affects gene expression and could possibly serve as a non-invasive method for early detection of breast cancer.8 DNA methylation is the addition of a methyl group (CH3) to the DNA strand which often modifies the expression of the genes, thus altering its function.9 Participants of this study included part of the population used in the Sister Study. Participants were broken down to categories for a case cohort and a sub cohort study. Candidate gene selection was based on the VD receptor, VD binding protein gene, GC, and genes directly involved in VD metabolism. One hundred ninety-eight participants were eligible within the two categories and serum 25-OHD was assessed along with methylation on their vitamin D-related genes. Results showed that 18 out of the 198 gene selected candidates indicated larger concentrations of serum 25-OH D to affect breast cancer risk.4 In conclusion with this study, 25-OH D concentrations were associated with DNA methylation with certain vitamin D genes, which could potentially lead to links of immune function-related genes that could interact to affect the risk of breast cancer.8
As the above studies reveal some associations between breast cancer and VD, data is still varied to determine a definite conclusion that VD deficiency is related to breast cancer. Although four studies correlated with the hypothesis that increasing vitamin D may decrease breast cancer risk, there are several limitations throughout the studies, such as a small population and duration of the studies that affect the credibility of these studies. Because of the limitations in research with such common disease, more research is needed.
Despite these research gaps, it was noted throughout some of the studies that while participants increased their vitamin D intake, it decreased their chances of breast cancer.4,5,6,7,8, Vitamin D has been proven to have immune-related properties to combat certain diseases, since this vitamin plays a role in the immune system.3 Therefore, it is still important for women and medical professionals to approach VD levels regularly, either through supplementation, sun exposure, or VD fortified foods. There is sufficient evidence to assume that vitamin D plays a role in prevention of breast cancer.