cadmium ( cd ) is often the result of environmental pollution caused by industrial and agricultural activities and it is widely dispersed into the environment ; hence , humans are exposed to it ubiquitously . an earlier study showed that cd acts as a stressor and leads to metabolic alterations . humans always come into contact with cd by occupational exposure , smoking , or diet . however , diet is the primary way cd enters the bodies of those without occupational exposure and who do not live in cd - polluted regions . it has been reported that dietary cd exposure is mainly from the relatively high cd content of agricultural crops and their products , such as rice , bread , potatoes , and vegetables . after entering the human body , the long - time biological effect of cd is that it may be a carcinogen . in 2008 , a population - based cohort study suggested that chronic dietary cd intake could increase risk of hormone - related cancers . similarly , another population - based prospective cohort study reported that dietary cd intake played an important role in prostate cancer development . thus , dietary cd intake may be associated with hormone - related cancers . for women , bc is an estrogen - related cancer , and a laboratory study indicated that cd could malignantly transform breast cells , stimulate breast cell proliferation , and inhibit apoptosis . the relationship between dietary cd exposure and bc risk has been supported by some observational studies , but the results of these studies were inconsistent [ 1013 ] , hence , a meta - analysis was conducted by cho et al . to clarify these inconsistent results , and this study found that there was a significant positive relationship between dietary cd intake and bc risk . recently , 2 recent prospective cohort studies have observed a relationship between dietary cd intake and bc risk ; however , neither of these studies found that dietary cd intake was a risk for bc . thus , we performed a meta - analysis to update and quantitatively re - assess the association between dietary cd exposure and the risk of bc by summarizing the inconsistent results of all published studies . thus , we intended to provide the best available evidence as to whether dietary cd exposure is a risk of bc . we searched pubmed , medline , and embase to identify studies on the relationship between dietary cd exposure and risk of bc , published through september 2014 . the following search terms were used in the searching strategy :  cadmium  combined with  breast cancer  and  breast carcinoma  . in addition , references cited within relevant reviews were retrieved , and we contacted the authors for useful information . we included studies that met the following criteria : 1 ) study designed as case - control or cohort study ; 2 ) the exposure of interest was dietary cd exposure ; 3 ) the outcome was bc incidence ; and 4 ) rr and corresponding 95% ci for the highest compared with the lowest of dietary cd exposure were reported . initially , we reviewed the titles and abstracts to ascertain reports of interest ; if uncertain , a subsequent full - text assessment was conducted . we extracted the following contents : the first author s surname , publication year , geographic area , age of the participants , number of cases and participants or controls , study design , range of cd exposure ; rr ( 95% ci ) for the highest vs. the lowest dietary cd exposure and variables used in a multivariate model . the key components of designs ( e.g. , selection of study populations , ascertainment of exposure and outcome , duration of follow - up ) were used to estimate the quality of primary studies , rather than reporting the aggregate scores . rr and the 95% ci were used to measure the association of dietary cd exposure and the risk of bc . homogeneity test was performed with the use of q statistic and i statistic , and subgroups analysis was used to identify the source of heterogeneity . sensitivity analysis was used to assess the influence of a single study on the overall risk estimate . publication bias was detected by begg s and egger s test , if the p - value was less than 0.05 , it was considered as statistically significant . we searched pubmed , medline , and embase to identify studies on the relationship between dietary cd exposure and risk of bc , published through september 2014 . the following search terms were used in the searching strategy :  cadmium  combined with  breast cancer  and  breast carcinoma  . in addition , references cited within relevant reviews were retrieved , and we contacted the authors for useful information . we included studies that met the following criteria : 1 ) study designed as case - control or cohort study ; 2 ) the exposure of interest was dietary cd exposure ; 3 ) the outcome was bc incidence ; and 4 ) rr and corresponding 95% ci for the highest compared with the lowest of dietary cd exposure were reported . initially , we reviewed the titles and abstracts to ascertain reports of interest ; if uncertain , a subsequent full - text assessment was conducted . we extracted the following contents : the first author s surname , publication year , geographic area , age of the participants , number of cases and participants or controls , study design , range of cd exposure ; rr ( 95% ci ) for the highest vs. the lowest dietary cd exposure and variables used in a multivariate model . the key components of designs ( e.g. , selection of study populations , ascertainment of exposure and outcome , duration of follow - up ) were used to estimate the quality of primary studies , rather than reporting the aggregate scores . rr and the 95% ci were used to measure the association of dietary cd exposure and the risk of bc . homogeneity test was performed with the use of q statistic and i statistic , and subgroups analysis was used to identify the source of heterogeneity . sensitivity analysis was used to assess the influence of a single study on the overall risk estimate . publication bias was detected by begg s and egger s test , if the p - value was less than 0.05 , it was considered as statistically significant . we initially identified 224 potential articles from the databases . after screening the abstracts and titles , most of these were excluded because they were reviews , the exposure or outcome did not relate to our analysis , or they were laboratory studies . overall , we identified 6 studies involving 321 315 participants and 11 978 cases [ 1013,15,16 ] . 2 were performed in europe , 2 in the usa , and 2 in japan . in addition , 5 studies were cohort studies [ 1012,15,16 ] and one was designed as case - control study . five results of these studies were reported by menopausal status in 4 studies , 4 results were conducted in postmenopausal women , and only 1 in premenopausal women . data of these 6 studies were analyzed in a random - effects model to estimate the relationship between dietary ca exposure and bc risk . in our study , there was no statistically significant positive association between dietary cd exposure and bc , and the combined rr and corresponding 95% ci was 1.01 [ 0.88 , 1.14 ] . figure 2 presents the results of our meta - analysis . according to menopause status , geographic area , and study design , we conducted subgroup - analysis to identify the source of heterogeneity . evidence of heterogeneity was also found across the 2 european studies and the cohort design studies . however , among these 3 subgroups , no significant positive correlation between dietary cd exposure and bc risk was found . sensitivity analysis was conducted to estimate the influence of each individual study on combined rr by removing 1 study at a time . the combined rrs were similar with one another , and no single study significantly changed the combined result , which indicated that the result was statistically stable and reliable . publication bias was detected based in the shape of funnel plots and by begg s and egger s tests . begg s funnel plot and egger s regression test showed a low probability of publication bias ( p=0.909 ) . we initially identified 224 potential articles from the databases . after screening the abstracts and titles , most of these were excluded because they were reviews , the exposure or outcome did not relate to our analysis , or they were laboratory studies . overall , we identified 6 studies involving 321 315 participants and 11 978 cases [ 1013,15,16 ] . 2 were performed in europe , 2 in the usa , and 2 in japan . in addition , 5 studies were cohort studies [ 1012,15,16 ] and one was designed as case - control study . five results of these studies were reported by menopausal status in 4 studies , 4 results were conducted in postmenopausal women , and only 1 in premenopausal women . data of these 6 studies were analyzed in a random - effects model to estimate the relationship between dietary ca exposure and bc risk . in our study , there was no statistically significant positive association between dietary cd exposure and bc , and the combined rr and corresponding 95% ci was 1.01 [ 0.88 , 1.14 ] . according to menopause status , geographic area , and study design , we conducted subgroup - analysis to identify the source of heterogeneity . evidence of heterogeneity was also found across the 2 european studies and the cohort design studies . however , among these 3 subgroups , no significant positive correlation between dietary cd exposure and bc risk was found . sensitivity analysis was conducted to estimate the influence of each individual study on combined rr by removing 1 study at a time . the combined rrs were similar with one another , and no single study significantly changed the combined result , which indicated that the result was statistically stable and reliable . publication bias was detected based in the shape of funnel plots and by begg s and egger s tests . begg s funnel plot and egger s regression test showed a low probability of publication bias ( p=0.909 ) . our study did not show a statistically significant positive association between dietary cd exposure and bc risk for the highest compared with the lowest category of dietary cd exposure , and the combined rr(95% ci ) of bc was 1.01 [ 0.88 , 1.14 ] . heterogeneity appears in a meta - analysis when the included studies have inconsistent conditions . in our study , evidence of heterogeneity was observed ; thus , we conducted subgroup - analysis to identify the source of heterogeneity . table 2 shows that the 2 european studies   were the main source of heterogeneity . julin et al . adjusted for a wide range of potential confounders for bc : age , height , bmi , education , use of oral contraceptives and postmenopausal hormones , age at menarche , age at first birth , alcohol consumption , glycemic load , total energy intake , and dietary intake of whole vegetables and grains ; however , the danish study of postmenopausal women adjusted for a relatively narrow range , not including age , total energy intake , or dietary intake of whole vegetables and grains . the relationship between cd exposure and bc risk has been investigated to assess whether cd has any modifying effects on the etiology and process of bc . these studies investigated women who were exposed to cd occupationally and who lived in cd - polluted areas ; a significant increase in frequencies of bc in cd - exposed women was found by a meta - analysis and systematic review . however , diet is the primary way cd enters the human body among populations without occupational exposure and who do not live in cd - polluted areas . the relationship between dietary cd exposure and bc risk also was considered in recent years . in our meta - analysis , 6 studies on this topic were identified , but the results were inconsistent . in 2012 , adams et al . conducted a cohort study to examine whether dietary cd exposure increased risk of bc , and the result showed no significant association . however , a swedish population - based prospective cohort study including 55 987 participants and 2112 patients showed that dietary cd intake increased risk of postmenopausal bc . the 2 japanese studies reported no significant positive relationships between dietary cd exposure and bc risk , but the case - control study found a statistically significant association for estrogen receptor - positive tumors among postmenopausal women . in 2013 , a meta - analysis of the relationship between dietary cd intake and cancer risk was conducted by cho et al . , who reported a significant association between dietary cd exposure and bc risk , and found that dietary cd intake increased risk of bc  the rr ( 95% ci ) was 1.15 [ 1.041.28 ] . however , in 2014 , a prospective cohort study in danish postmenopausal women did not support the above result and reported that dietary cd intake was not linked to the risk of bc or other hormone - related cancers . similarly , another cohort study indicated dietary cd intake had no statistical association with cancer risk . thus , we performed a meta - analysis to update and quantitatively re - assess this relationship and we did not find a statistically significant positive association between dietary cd exposure and bc risk . the subgroup - analysis of our study was conducted at the same time and no significant positive association between dietary cd exposure and bc risk was found in any subgroups . cd acts as a metallo - estrogen and may play an important role in the estrogenic signaling pathway ; it can malignantly transform breast cells , stimulate breast cell proliferation , and inhibit apoptosis . in addition , cd also can induce bc by a non - estrogen - related mechanism . it can change normal breast epithelial cells into a basal - like breast carcinoma characterized by negativity of the er - a and the epidermal growth factor receptor 2 ( her2 ) , leading to reduced expression of bc susceptibility gene 1 , and increasing the expression of cytokeratin 5 and p63 . although our study did not find a statistically significant positive association between dietary cd exposure and bc risk , many factors that may influence this association should be considered . reported that iron deficiency led to increased absorption of cd in animal and human studies . in addition , zinc can limit absorption of cd by decreasing in the intracellular cd accumulation and by the sequestration of cd by cd - induced metallothionein . second , different types of diet may influence the bioavailability and/or kinetics of dietary cd . for example , the swedish prospective cohort study showed that the low cd and high whole grain and vegetables intake groups had the lowest risk , but they had the highest risk of bc in relation to diets high in cd and low in whole grains and vegetables , which is why these food have a conflicting roles in the development of bc because whole grains and vegetables are relatively cd - rich foods . for example , average urine cd concentration in never - smokers was lower than that in smokers . in our study , only 2 investigations reported a relationship between dietary cd exposure and bc risk in smokers and never - smokers , but no study showed a positive association . our meta - analysis of 6 studies involving 321 315 participants and 11 978 cases improved the statistical power and found a more reliable result of the association between dietary cd exposure and bc risk . first , other factors may influence this association and the effect of dietary cd exposure on the development of bc . although most included studies adjusted for a wide range of factors , some studies did not exclude the potential factors . second , in all included studies , cd exposure was assessed with a food frequency questionnaire ( ffq ) , so measurement error in individual studies might have led to incorrect classification of cd exposure . third , none of the included studies reported whether the participants lived in a polluted area and , if so , for how long before the primary studies were started . fourth , the inclusion criteria might induce selection bias and potential publication bias still existed . fourth , all of our included studies were conducted in developed countries , and other studies in less - developed countries are warranted . our study did not find a statistically significant positive association between dietary cd exposure and bc risk . it is necessary to investigate this potential relationship among high - risk groups and more cohort studies based on diverse populations are needed .