Tehran, a metropolitan city with a population of more than 10 million, is one the most pollutant area throughout the world. Air pollution is a life-threating factor caused by urbanization and industrialization, especially due to vehicle fuel. Therefore, it seems traffic congestion is a common source of Pb emission to the environment (Ali asghar, 2021; Kermani, Dowlati, Jonidi jafari, & Rezaei Kalantary, 2016; Khorrami et al., 2021).
Pb is used widely in the industry and domestic settings, however, women could possibly more exposed to Pb via ambient environment, cooking and cosmetics. Lead (Pb) is studied to be toxic for multiple organs and may contribute to malignancies at even a low dose after a long-term exposure. Many studies have confirmed a link between Pb exposure and human cancerous alterations in liver, kidney and brain for their sensitivity to Pb toxicity. Specifically, Smoking women have a higher Pb concentration in the endo-cervical tissues than non-smoking women. However, there is not a significant association between Pb and cervical cancer and the Pb effect on women malignancies is unknown. Elevated blood Pb level is known to be detrimental on reproductive health, birth outcomes and hormonal functions. Pb potential carcinogenic mechanism is not fully understood yet. However, some evidences demonstrated an excess Pb replaces zinc in some regulatory proteins, thus it can be accumulated in blood cell and therefore be transported to other organs in animal model. Pb could cause direct DNA damage by inducing free radicals that causes oxidative stress damage for DNA and chromosomal. Notably, its tumorigenesis effect lies in its supportive ability to impair DNA synthesis and repair system. Therefore, the synergetic effect between Pb and other carcinogens, particularly Cadmium, for the origination of tumours in cervix, may be considered in further studies (Caffo et al., 2014; Fenga, Gangemi, Di Salvatore, Falzone, & Libra, 2017; Kumar, 2018; Marouf, 2018; Matovic, Buha, Ethukic-Cosic, & Bulat, 2015; Rzymski et al., 2016; Sanders et al., 2015; Silbergeld, 2003; Silbergeld, Waalkes, & Rice, 2000; Wilk et al., 2017).
The microbial pathogens might also play a synergistic role in the progression of cervical cancer in the existence of carcinogenic heavy metals and trace elements. The scientific literatures suggested Pb is associated with change of miRNA expression in cervix through epigenetic regulations, immunotoxin effects by dysregulating cytokine productions, promoting inflammation, and altering the expression and activity of T helper cells (Fenga et al., 2017; Rzymski et al., 2016). Nevertheless, none of the proposed mechanism could fully explain the carcinogenic role of Pb or its differential expressions in multiple organs, further studies are still needed. In line with our results, a previous study also reported a higher Pb level in CIN endocervical tissues, compared to histological normal tissues. Notably, their study had 3 CIN cases, while our study focused on bigger sample size, ensuring a better statistical power(Rzymski et al., 2016; Sanders et al., 2015).
Our study adds up to the direct evidence that higher Pb level accumulated in the cervical tissue is associated with higher risk of cancerous changes. There are also significant drawbacks in our study. Firstly, our study could not exclude the effects of factors that may affect Pb exposure such as smoking habits, education, living conditions and working environment. Albeit, smoking habit in not common in Iranian women. We considered the education, smoking habits and environment variables in the questionnaire, but they have not been filled in that, so the insufficient factors excluded for biostatical analysis. Secondly, for the cross-sectional setting of the study design, we could not elucidate the possible causal relationship between Pb exposure and cervical cancer. It could be Pb triggered cancerous changes in the organ, but it can also be the cancerous changes in the cells increased the affinity between Pb and cervical tissues.