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Eurasian Journal of
Medicine and Oncology Vitamin D and breast cancer
incidence rate of 54.1/100,000. That year, the number of the Iranian population showed that Vitamin D deficiency
deaths due to breast cancer worldwide was about 666,000, was not associated with the development of breast cancer.
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placing it fourth among all cancers. It is estimated that Similarly, no significant association was observed between
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by 2050, there will be about 3.2 million new cases per Vitamin D intake and breast cancer. One study confirms
year. The prevention and treatment of breast cancer hold that the protective effect of Vitamin D on breast cancer risk
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extremely critical significance and far-reaching value at the may have been overestimated in previous observational
societal level. Vitamin D is a fat-soluble vitamin derived studies. 25
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from steroids. It has a wide range of biological activities Given that most of the traditional epidemiological
in various tissues of the human body. It plays a role in studies are observational and susceptible to confounding
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bone homeostasis and the regulation of multiple systemic factors, there is a certain bias in the interpretation of
metabolic pathways. 8,9 the results. To address this issue, we used Mendelian
Although many researchers around the world have randomization (MR) in our study. The basic principle of
discussed and studied the association between Vitamin D MR is derived from Mendel’s laws of inheritance – gametes
and breast cancer, the relationship between the two is still are randomly assigned by their parents following the
inconclusive. Some epidemiological studies have shown offspring allele during the formation process. The genes
that the incidence of breast cancer is inversely correlated are randomly assigned to the population before a person
with Vitamin D levels. 10-15 Relevant case–control studies is born, and the phenotype determined by the genes is also
and prospective studies have also confirmed that the intake randomly assigned. MR is an epidemiological technique
of Vitamin D is negatively correlated with breast cancer. 16-18 that uses instrumental variable analysis to infer a causal
A prospective study in Black women showed that moderate relationship between exposure and the results of the
Vitamin D supplementation was associated with a reduced use of genetic variation, particularly single nucleotide
risk of triple-negative breast cancer. In an observational polymorphisms (SNPs). Based on the principle of random
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data meta-analysis, Vitamin D supplementation was combination of genotypes during meiosis, the MR method
inversely related to the risk of breast cancer and was more can prevent reverse causal bias and limit confounders.
protective at doses >10 μg/day. Although these findings The exposure and outcome data of the two-sample MR
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suggest potential positive effects of Vitamin D on breast analysis were derived from two different genome-wide
cancer, rash conclusions should not be drawn. The human association studies (GWAS) datasets, or the aggregation of
body is complex and is influenced by multiple factors. multiple GWAS datasets; hence, the test efficiency of the
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There may be undiscovered factors interfering with or results could be improved. Therefore, the two-sample MR
regulating the relationship between Vitamin D and breast study is more reliable than the traditional epidemiological
cancer, which can vary by ethnicity, geography, lifestyle, and approach.
genetic background. This complexity necessitates follow-up
research, along with more in-depth and comprehensive 2. Materials and methods
studies, to further clarify their relationship. Vitamin D may 2.1. Assumptions underlying MR
be a potential key to preventing and treating breast cancer, MR is a strategy for epidemiological studies that uses
but more research is needed to understand its actual role in genetic variation as an instrumental variable to assess
this complex disease. At the same time, the comprehensive causal associations between specific exposure factors and
prevention and control of breast cancer requires a health outcomes. Originating in the field of econometrics,
coordinated effort across all sectors of society. This includes the core of this method is the use of instrumental variables
raising awareness of women’s health, enhancing early to infer causal effects in the presence of unobserved
screening programs, and improving the medical security confounders. Three key prerequisites must be met when
system to ensure better protection for women’s health. using genetic variation as an instrumental variable: (i) the
However, some studies have shown that Vitamin D selected genetic variant must be significantly associated
levels are not associated with breast cancer. 21,22 One of the with the exposure factors in the study, (ii) these genetic
studies, believed to be the largest to date in this direction, variants should remain independent of any confounding
examined the association of dietary Vitamin D intake with factors that may affect the relationship between exposure
breast cancer risk in the European Prospective Survey and outcome, and (iii) genetic variation can only indirectly
of Cancer and Nutrition. During an average follow-up affect the outcome by influencing the exposure factors,
of 8.8 years, they found no evidence of an association that is, there is no other path that directly affects the
between Vitamin D intake and breast cancer risk in this outcome. In this study, we collected and analyzed detailed
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large prospective cohort. In addition, another study in confounding factors for the study population, including
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Volume 9 Issue 3 (2025) 101 doi: 10.36922/EJMO025130064

