Breast Cancer Frequency and Exposure to Cadmium: A Meta-Analysis and Systematic Review

  • Rahim, Fakher (Toxicology Research Center, School of Pharmacy, Jundishapur University of Medical Sciences) ;
  • Jalali, Amir (Toxicology Research Center, School of Pharmacy, Jundishapur University of Medical Sciences) ;
  • Tangestani, Raheleh (Toxicology Research Center, School of Pharmacy, Jundishapur University of Medical Sciences)
  • Published : 2013.07.30


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.


Cadmium;breast cancer;meta-analysis;systematic review


  1. Adams SV, Newcomb PA, White E (2012). Dietary cadmium and risk of invasive postmenopausal breast cancer in the VITAL cohort. Cancer Causes Control, 23, 845-54.
  2. Akesson A, Julin B, Wolk A (2008). Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res, 68, 6435-41.
  3. Antila E, Mussalo-Rauhamaa H, Kantola M, Atroshi F, Westermarck T (1996). Association of cadmium with human breast cancer. Sci Total Environ, 186, 251-6.
  4. Benderli Cihan Y, Sozen S, Ozturk Yildirim S (2011). Trace elements and heavy metals in hair of stage III breast cancer patients. Biol Trace Elem Res, 144, 360-79.
  5. Brama M, Gnessi L, Basciani S, et al (2007). Cadmium induces mitogenic signaling in breast cancer cell by an ERalphadependent mechanism. Mol Cell Endocrinol, 264, 102-8.
  6. Chen YC, Pu YS, Wu HC, et al (2009). Cadmium burden and the risk and phenotype of prostate cancer. BMC Cancer, 9, 429.
  7. Freisinger E, Vasak M (2013). Cadmium in metallothioneins. Met Ions Life Sci, 11, 339-71.
  8. Fujishiro H, Yano Y, Takada Y, Tanihara M, Himeno S (2012). Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics, 4, 700-8.
  9. Gallagher CM, Chen JJ, Kovach JS (2010). Environmental cadmium and breast cancer risk. Aging (Albany NY), 2, 804-14.
  10. Govil PK, Sorlie JE, Murthy NN, et al (2008). Soil contamination of heavy metals in the Katedan Industrial Development Area, Hyderabad, India. Environ Monit Assess, 140, 313-23.
  11. Hellstrom L, Persson B, Brudin L, et al (2007). Cadmium exposure pathways in a population living near a battery plant. Sci Total Environ, 373, 447-55.
  12. Hjortenkrans D, Bergback B, Haggerud A (2006). New metal emission patterns in road traffic environments. Environ Monit Assess, 117, 85-98.
  13. Ionescu JG, Novotny J, Stejskal V, et al (2006). Increased levels of transition metals in breast cancer tissue. Neuro Endocrinol Lett, 27, 36-9.
  14. Jarup L, Akesson A (2009). Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol, 238, 201-8.
  15. Jarup L (2003). Hazards of heavy metal contamination. Bri Med Bull, 68, 167-82.
  16. Jin YH, Clark AB, Slebos RJ, et al (2003). Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet, 34, 326-9.
  17. Johnson MD, Kenney N, Stoica A, et al (2003). Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med, 9, 1081-4.
  18. Joseph P, Muchnok TK, Klishis ML, et al (2001). Cadmiuminduced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun, and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species. Toxicol Sci, 61, 295-303.
  19. Julin B, Wolk A, Bergkvist L, Bottai M, Akesson A (2012). Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study. Cancer Res, 72, 1459-66.
  20. Julin B, Wolk A, Johansson JE, et al (2012). Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study. Bri J Cancer, 107, 895-900.
  21. Kok M, Linn SC (2010). Gene expression profiles of the oestrogen receptor in breast cancer. Neth J Med, 68, 291-302.
  22. Kotsopoulos J, Sukiennicki G, Muszynska M, et al (2012). Plasma micronutrients, trace elements, and breast cancer in BRCA1 mutation carriers: an exploratory study. Cancer Causes Control, 23, 1065-74.
  23. Linsak DT, Linsak Z, Spiric Z, et al (2013). Influence of cadmium on metallothionein expression and products of lipid peroxidation in the organs of hares (Lepus europaeus Pallas). J Appl Toxicol, [Epub ahead of print].
  24. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (2006). Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet, 367, 1747-57.
  25. Luckett BG, Su LJ, Rood JC, Fontham ET (2012). Cadmium exposure and pancreatic cancer in south Louisiana. J Environ Public Health, 2012, 180186.
  26. McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006). Cadmium exposure and breast cancer risk. J Natl Cancer Inst, 98, 869-73.
  27. Nagata C, Nagao Y, Nakamura K, et al (2013). Cadmium exposure and the risk of breast cancer in Japanese women. Breast Cancer Res Treat, 138, 235-9.
  28. Ojajarvi IA, Partanen TJ, Ahlbom A, et al (2000). Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med, 57, 316-24.
  29. Pasha Q, Malik SA, Iqbal J, Shaheen N, Shah MH (2008). Comparative evaluation of trace metal distribution and correlation in human malignant and benign breast tissues. Biol Trace Elem Res, 125, 30-40.
  30. Peralta-Videa JR, Lopez ML, Narayan M, Saupe G, Gardea- Torresdey J (2009). The biochemistry of environmental heavy metal uptake by plants: implications for the food chain. Int J Biochem Cell Biol, 41, 1665-77.
  31. Safe S (2003). Cadmium's disguise dupes the estrogen receptor. Nat Med, 9, 1000-1.
  32. Saleh F, Behbehani A, Asfar S, Khan I, Ibrahim G (2011). Abnormal blood levels of trace elements and metals, DNA damage, and breast cancer in the state of Kuwait. Biol Trace Elem Res, 141, 96-109.
  33. Sawada N, Iwasaki M, Inoue M, et al (2012). Long-term dietary cadmium intake and cancer incidence. Epidemiology, 23, 368-76.
  34. Schwartz GG, Reis IM (2000). Is cadmium a cause of human pancreatic cancer? Cancer Epidemiol Biomarkers Prev, 9, 139-45.
  35. Shih CM, Ko WC, Wu JS, et al (2004). Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem, 91, 384-97.
  36. Strumylaite L, Bogusevicius A, Abdrachmanovas O, et al (2011). Cadmium concentration in biological media of breast cancer patients. Breast Cancer Res Treat, 125, 511-7.
  37. Strumylaite L, Bogusevicius A, Ryselis S, et al (2008). Association between cadmium and breast cancer. Medicina (Kaunas), 44, 415-20.
  38. Tekin D, Kayaalti Z, Aliyev V, Soylemezoglu T (2012). The effects of metallothionein 2A polymorphism on placental cadmium accumulation: Is metallothionein a modifiying factor in transfer of micronutrients to the fetus? J Appl Toxicol, 32, 270-5.
  39. Templeton DM, Liu Y (2010). Multiple roles of cadmium in cell death and survival. Chem Biol Interact, 188, 267-75.
  40. Thevenod F, Lee WK (2013). Toxicology of cadmium and its damage to Mammalian organs. Met Ions Life Sci, 11, 415-90.
  41. Wu HD, Chou SY, Chen DR, Kuo HW (2006). Differentiation of serum levels of trace elements in normal and malignant breast patients. Biol Trace Elem Res, 113, 9-18.

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