In the past few decades, with urbanization and industrialization levels continue to rise, environmental pollution has become a worldwide problem. Endocrine disrupting chemicals (EDCs), which can be found in agriculture and industry, have been proved to affect hormone synthesis, metabolism and function(Ma et al.2019). Bisphenol, as a widely used EDC, can be found in plastics, receipts, food packaging, and other products. regulate hormone signal paths and various other biological functions in a wide range of products (Murata et al. 2017). Relevant studies have shown that EDs can interact with some endocrine signaling pathways, such as estrogen receptor (Legeay et al. 2017). Estrogen receptor can regulate estrogen synthesis and related enzyme activities by transcription factors. Classical estrogen receptors include two subtypes of ERα and ERβ, both of which have similar structures. ERα is mainly expressed in hormone-targeted tissues, such as breast, uterus, testes and ovaries. On the contrary, ERβ is mainly expressed in the prostate, bladder, lung and intestine (Rochester et al. 2015).
In the past 40 years, the incidence and mortality of tumors have been increasing. As is estimated by the American Cancer Society, more than 1.7 million new cancers will be diagnosed in 2019, and there will be approximately 607,000 cancer-related deaths (Giri et al. 2020). Prostate cancer is one of the most common malignant tumors and the leading cause of cancer death in men. As is reported, prostate cancer comes in the second place after lung cancer in men (Labbé et al. 2018). In addition to age, race and family history of prostate cancer, prostate cancer susceptibility genes are also a key factor in the development of prostate cancer (Sathianathen et al. 2018). Relevant studies have confirmed that some DNA repair genes, including CHEK2, PALB2, BRIP1 and NBS1, may lead to a higher risk of prostate cancer. The risk assessment of prostate cancer usually combines the patient’s age, clinical tumor stage, serum PSA concentration, and Gleason score for a comprehensive analysis (Barata et al. 2019). Among them, EDCs play a key role in the occurrence and development of prostate cancer (Hu et al. 2012). Androgen receptor (AR) is very important for prostate development and tumorigenic growth. A large amount of evidence demonstrated that human exposure to EDCs can change the function of hormones, and finally promote the occurrence and development of prostate cancer (Litwin et al. 2017). As an endocrine disruptor that interact with hormone, BPA can directly interact with both ER-α and ER-β and may enhance prostate cancer growth (Shafei et al. 2018). Besides, patients with prostate cancer showed higher levels of BPA in their urine, which suggests that urine BPA levels may have prognostic value for prostate cancer (Hess-Wilson. 2005). As an alternative for BPA, BPS has been increasingly detected in consumer products, foodstuffs, water, sediment and sludge in recent years (Fossati et al. 2016). Studies have reported the occurrence of BPS in human urine, among 315 urine samples collected from the United States, BPS was found in 81% of the total samples, and the average concentration of BPS was 0.17 ng/ml, which indicated that BPS may have toxic effects on the genitourinary system (Eladak et al. 2014).
Although the epidemiological literature on the toxicity of BPS are growing rapidly, however, its quantity and quality are still limited. Many studies are essentially cross-sectional studies, which makes results difficult to verify. The Comparative Toxicogenomics Database (CTD) is a literature-based and manually curated public resource and give us advance understanding regarding the effect of environmental exposure on human health. Besides, two tumor databases are also applied for further analysis. The Cancer Genome Atlas (TCGA), as a landmark cancer genomics program, molecularly characterized over 20,000 primary cancer and matched normal samples spanning 33 cancer types. GEO is a public functional genomics data repository supporting MIAME-compliant data submissions and provide array-based and sequence-based data. The development of prostate cancer involves the damages to the normal prostate transcription network. Here, we evaluate the key genes that associated with prostate cancer. Besides, the interaction of toxins with their interaction genes helps understand the multiple pharmacology of bisphenols and their effects on biological networks. TCGA and GEO database were applied to explored the possible mechanism underlying the association between prostate cancer and bisphenols-exposure.