Cadmium and Other Metals
CATEGORY*: IARC known, NTP known
USED IN: Some cosmetics, dental fillings, paints, electronics batteries, manufacturing
THE GIST: Cadmium enters our blood streams via food, water and air. Cigarette smoke contains high levels of cadmium, which has been linked to early-onset puberty—a risk factor for breast cancer. The metal also transforms healthy breast cells into cells with a cancer-like profile. Other metals to be wary of include iron, nickel, chromium, zinc and mercury.
State of the Evidence on Cadmium and Other Metals
Higher accumulations of iron, nickel, chromium, zinc, cadmium, mercury and lead have been found in cancerous breast biopsies as opposed to biopsies taken from the breasts of women without breast cancer. These metals also have been found in higher concentrations in blood serum samples from women diagnosed with cancer as compared with those from healthy women (Ionescu, 2006; Wu, 2006).
TIPS FOR PREVENTION
Store substances that contain cadmium safely away and keep nickel-cadmium batteries out of reach of young children. Do not put nickel-cadmium batteries in the trash, but rather look for special battery recycling or disposal centers in your community.More tips for protecting yourself and the environment >
Laboratory studies have shown that a number of metals including copper, cobalt, nickel, lead, mercury, methylmercury, tin, cadmium and chromium have estrogenic effects on human breast cancer cells (MCF-7 cells) cultured in vitro (Brama, 2007; Martin, 2003; Sukocheva, 2005), with cadmium expressing the highest level of estrogenic activity (Choe, 2003).
Epidemiological studies have demonstrated an association between higher cadmium levels in urine (Gallagher, 2010; McElroy, 2006) or blood (Saleh, 2011) and increased breast cancer risk. Prospective studies of women’s dietary intake of cadmium and later diagnosis of cancers observed a statistically significant relationship between higher levels of dietary cadmium exposure and incidence of both endometrial cancers (Akesson, 2008) and post-menopausal breast cancers (Julin, 2012). With regard to breast cancer, the effect was significant for all cancers combined, but more pronounced for estrogen-receptor-positive (ER+) tumors (Julin, 2012). On the other hand, a recent study examining dietary cadmium intake in Japanese people and risk for total cancers and individual cancers, including breast cancer, found no relationship (Sawada 2012). A recent study in the United States that looked at dietary cadmium levels and breast cancer risk also did not find a relationship (Adams, 2012). Methodological differences between studies, especially in the method by which dietary cadmium is estimated, may account for the differences in findings across studies (Adams, 2012).
In young rats, treatment with low doses of cadmium led to an increase in branching and bud formation in mammary tissue, and the synthesis of several estrogen-associated proteins. Prenatal exposure of rats to cadmium led to early onset of puberty and greater numbers of mammary terminal end buds, both known risk factors for breast cancer (Johnson, 2003).
Estrogenic effects of cadmium have been studied in some detail, and the metal has been shown to interfere with a number of normal estrogen-sensitive pathways (Byrne, 2009). Cadmium may bind to and activate mammary cell estrogen receptors; it also interacts with and regulates the transcription of estrogen-dependent genes affecting the synthesis of proteins and/or the activity of cell-signaling pathways in ways similar to the natural estrogen estradiol (Silva, 2012). Nevertheless, some of the estrogen-mimicking effects of cadmium are most likely resulting through mechanisms other than those regulated by steroidal estrogens (Ali 2010; Ali 2012).
In addition to its endocrine effects on mammary tumor cells, cadmium transforms healthy breast epithelial cells into cells with a cancer-like profile through non-hormone-related pathways. Thus, in the presence of cadmium, the cells have altered gene expression and DNA changes in DNA methylation (an epigenetic change) that are typical of cells undergoing transformation from healthy to cancerous cells (Benbrahim-Tallaa, 2009).
Like another estrogen-mimicking endocrine disruptor, bisphenol A, cadmium interferes with the efficacy of a common chemotherapeutic agent often prescribed for women who have been diagnosed with breast cancer. In a study examining the effects of cadmium, 5-fluorouracil (5-FU), and the two combined on the viability of cultured MCF-7 breast cancer cells, co-administration of cadmium negated the anti-cancer effects of 5-FU (Asara, 2012).
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.