Cadmium (Cd) is well known as a heavy metal used in our daily life, occupational and environmental exposure to which is harmful to the human body. Cd is toxic even at low exposure levels, and has acute and chronic effects on health and the environment [1]. Since Cd is not biodegradable, it remains in circulation once released into the environment [2-4]. The routes through which humans are exposed to Cd are commonly categorized as occupational exposure and environmental exposure (non-occupational exposure). The occupational route involves exposure to Cd by the mining, production, and consumption of non-ferrous metal or plating, welding, the utilization of storage batteries and agricultural chemicals, and pesticide production [5]. Environmental exposure to Cd most often occurs through food intake such as meat, shellfish, vegetables, and any form of food whose packaging contains Cd; moreover, exposure to cigarette smoking and dust from polluted soil are routes of chronic exposure [6,7]. In Korea, smoking prevalence was extremely high in the 2000s. According to a report by Jee et al. [7], the prevalence of smoking among males in Korea in 2000 was 68%. Furthermore, rice consumption is considered to be a major factor associated with high Cd levels in Asian countries, including Korea [8].

The environmental route usually involves lower levels of exposure, and therefore a lower risk of resulting disease, than occupational exposure. However, some health effects have been reported to be associated with low-level exposure, such as blood pressure elevation and kidney function degradation. Furthermore, since environmental exposure to Cd involves numerous aspects of daily activities, is globally recognized as a public health hazard, and may disproportionately affect vulnerable groups such as children, pregnant females, and the elderly, the potential effects of Cd exposure should be a concern from a public health perspective.

However, few studies have examined the associations of socioeconomic variables such as income level, education level, and occupation with Cd levels, together with an analysis of the possible confounding effect of smoking.

In this analysis of cross-sectional data from the KNHANES, we aimed to explain the association between blood Cd levels and income using a modeling method in which factors related to Cd levels, such as sex, smoking status, education, and occupation, were added step by step. Blood Cd levels were significantly higher among those with low income and less formal education. However, these associations were substantially attenuated after controlling for smoking status, although they still remained present. The results of this study suggest that blood Cd levels may also be a biomarker reflecting socioeconomic disparities. Moreover, interventions targeting Cd levels in individuals in the low-income and low-education groups who are highly exposed to Cd are needed. The results of our analysis correspond with existing results regarding health inequities and heavy metal exposure [9,10]. In this study, an association between income and blood Cd levels was found, but the magnitude of this association decreased from 0.126 to 0.050 in male and from 0.076 to 0.057 in female after controlling for smoking status. The sharp decrease in the magnitude of the association among male after controlling for smoking status seems to reflect the close association between smoking status and blood Cd levels. Therefore, the association between income and blood Cd levels can be interpreted as the result of confounding by smoking status. However, the relatively small decrease in the magnitude of the association among female after controlling for smoking could be interpreted in light of previous studies reporting the high prevalence in Cd level among female [13]. However, it seems more likely that the results in our study are due to the low reliability of self-reported smoking among female, as a previous study reported unrealistically low rates of smoking prevalence in Asian female due to under-reporting [14]. Although we replaced the self-reported smoking variable among female with urinary cotinine levels, the results were similar after controlling for urinary cotinine levels, which can be interpreted as indicating that confounding effect of urinary cotinine levels was lower among female than among male.

Therefore, smoking made a significant contribution to the association between income and blood Cd levels in male, but not in female. In order to analyze the remaining association between income and blood Cd levels, education level and occupation classification were additionally controlled. Doing so eliminated the association between income and blood Cd levels. Integrating these findings, the association between income and blood Cd levels appears to result from confounding by smoking status and education level.

Previous studies have investigated associations between smoking status and Cd exposure. According to a recent meta-analysis reported by Hecht et al. [15], the correlation coefficient between cigarette smoking and Cd levels was 0.540. The associations found between cigarette smoking and Cd levels were 0.546 in this study (0.663 in male and 0.316 in female). Moreover, the present study demonstrated this association not only with cigarette smoking as a self-reported categorical variable, but also with pack-years and urinary cotinine levels, making our results more sophisticated than those of previous studies.

Female tended to have higher blood Cd levels in this study, and several former studies have reported that the health effects of toxic metals differ in prevalence or manifest differently in male and female [13]. Vahter et al. [13] reported that Cd-related health effects were more common among female than male, and hypothesized that this may have been due to differences in sensitivity to toxic effects; however, it remains unclear whether that is the case, as it is possible that their findings merely reflected Itai-itai disease, which involves a combination of kidney damage, osteomalacia, and osteoporosis, is the most advanced form of Cd-induced disease, and it has been reported to be caused by consumption of rice that is heavily contaminated by Cd emitted from mines [16,17]. A previous study also found that Itai-itai disease more strongly affected elderly, multiparous female; however, the degree to which those findings could be interpreted as showing a causal relationship relevant for risk assessment is limited [18].

Several studies have reported that Cd exerts estrogenic effects [14-19]. Based on those results, Cd was found to mimic estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone-binding domain of the estrogen receptor [20].

One of the major strengths of this study is its use of the KNHANES, a representative data source. The KNHANES is a cross-sectional, nationally-representative survey of the general population in Korea, annually conducted by the KCDC as part of the Ministry of Health and Welfare. Although the design was cross-sectional, the risk of an inverse association was relatively low, because socioeconomic determinants are formed throughout a long-term period, and blood Cd accumulates for a long period in the human body. Although smoking is associated with both low socioeconomic status and blood Cd levels, the association between socioeconomic status and Cd levels remains unclear. In cross-sectional data from the KNHANES, blood Cd levels were significantly higher among those with a low income and less formal education. Smoking history contributed to these associations, but did not explain them entirely.