DOI:http://dx.doi.org/10.7314/APJCP.2013.14.7.4283 Breast Cancer Frequency and Exposure to Cadmium: a Meta-Analysis
RESEARCH ARTICLE Breast Cancer Frequency and Exposure to Cadmium: A MetaAnalysis and Systematic Review Fakher Rahim1*, Amir Jalali1,2, Raheleh Tangestani1 Abstract Background: In this meta-analysis we review evidence suggesting that exposure to cadmium is a cause of breast cancer. Materials and Methods: We conducted Medline/PubMed and Scopus searches using selected MeSH keywords to identify papers published from January 1, 1980 through January 1, 2013. Data were merged and summary mean differences were estimated using either a random-effects model or a fixed-effects model. Results: There were 13 studies including 978 exposed cases and 1,279 controls. There was no statistically significant difference in the frequencies of breast cancer between cadmium-exposed and control groups, and the summary estimate of mean difference was 0.71 (95%CI: 0.33-1.08). However, stratification showed that there were statistically significant differences in the frequencies of breast cancer between cadmium-exposed and control groups among Asian compared with Caucasian population, and the summary estimates of mean difference were 1.45 (95%CI: 0.62-2.28) vs. 0.25 (95%CI: -0.09-0.6), respectively. There was a difference in the frequencies of breast cancer between cadmium-exposed and control groups in peripheral venous blood sampling methods, and the summary estimate of mean difference was 1.41 (95%CI: 0.46-2.37). Conclusions: Data indicate that the frequencies of breast cancer might be an indicator of early genetic effects for cadmium-exposed populations. However, our meta-analysis was performed on population-based studies; meta-analysis based on individual data might provide more precise and reliable results. Therefore, it is necessary to construct an international database on genetic damage among populations exposed to cadmium that may contain all raw data of studies examining genetic toxicity. Keywords: Cadmium - breast cancer - meta-analysis - systematic review Asian Pac J Cancer Prev, 14 (7), 4283-4287
Introduction Cadmium (Cd) is a human carcinogenic heavy metal, which is taken up from contaminated soil by a variety of vegetables and grains, as a result of industrial and agricultural activities (Jarup, 2003; Hellstrom et al., 2007; Jarup and Akesson, 2009; Peralta-Videa et al., 2009). In the human body, most of the Cd is bounded to low molecular weight proteins functioning in the essential metals such as zinc called metallothioneins (Freisinger and Vasak, 2013; Linsak et al., 2013). The Cd-metallothioneins complex is dispersed to different organs and tissues, and is eventually reabsorbed in kidneys, so Cd accumulates in tissues because of absence of mechanism for the excretion of this heavy metal from the body (Fujishiro et al., 2012; Tekin et al., 2012). Epidemiological evidences reported the relationship of occupational and dietary Cd exposure with various cancers such as pancreatic cancer (Ojajarvi et al., 2000; Schwartz and Reis, 2000). The possible mechanisms for Cd-induced cancer include induction of oxidative stress (Joseph et al., 2001; Shih et al., 2004), inhibition of DNA damaging repair (Jin et al., 2003), and apoptosis inhibition (Templeton and Liu, 2010).
Estrogen receptor (ER) plays a crucial role between different signaling pathways in breast cancer (Kok and Linn, 2010), besides some experimental studies offer evidence that Cd may act as a metallo-estrogen through mimicking the effect of estrogen on mammary gland (Johnson et al., 2003; Safe, 2003), or induces mitogenic signaling (Brama et al., 2007). Breast cancer is the second leading cause of the dead after lung cancer, with nearly 1.4 million new cases (Lopez et al., 2006). A few small case–control studies supported the role of Cd exposure in the development of breast cancer so far (McElroy et al., 2006; Gallagher et al., 2010). Furthermore, a few cohorts suggested the role of dietary Cd in the breast cancer (Adams et al., 2012; Julin et al., 2012). In this meta-analysis we attempt to review evidence indicating that exposure to cadmium is a cause of breast cancer.
Materials and Methods Literature source and searching methods We conducted Medline/PubMed and Scopus searches using [“Cadmium” (Mesh) OR “Cadmium Chloride”
Toxicology Research Center, 2Department of Pharmacology and Toxicology, School of Pharmacy, Jundishapur University of Medical Sciences, Ahvaz, Iran *For correspondence:
[email protected] 1
Asian Pacific Journal of Cancer Prevention, Vol 14, 2013
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Asian Pacific Journal of Cancer Prevention, Vol 14, 2013
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