Infections with eleven species of pathogens associated with

Infections with eleven species of pathogens associated with cancers are classified as Group 1 carcinogens, definitely “carcinogenic to humans”, by the IARC. These agents include Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium, human papillomavirus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), human herpes virus type 8 (HHV-8) and human immunodeficiency virus type 1 (HIV-1) (Bouvard et al., 2009; IARC, 2012; de Martel et al., 2012). Among parasitic diseases, infections with the two fish-borne liver flukes of the family Opisthorchiidae (trematodes), specifically Opisthorchis viverrini and Clonorchis sinensis, can induce cholangiocarcinoma, and infection with the blood fluke Schistosoma haematobium may cause cancer of the urinary buy Plerixafor (Bouvard et al., 2009). Although malaria per se is not considered carcinogenic to humans by the IARC, the geographical association between the occurrence of malaria and that of Burkitt lymphoma provides a clue that malaria plays as a co-carcinogenic factor, together with EBV infection, for the development of Burkitt lymphoma (Molyneux et al., 2012). Other species of the genera Opisthorchis and Schistosoma are thought likely to be carcinogenic (Sripa et al., 2007; Pakharukova and Mordvinov, 2016). Intriguingly, Trypanosoma cruzi, the etiological agents of Chagas disease, displays apparently paradoxical roles in malignancy in exerting carcinogenic and anticancer properties (Krementsov, 2009; Sacerdote de et al., 1980). Potential causative roles of other parasitic infections have been postulated (Machicado and Marcos, 2016). Here, we summarize current concepts and facts on associations of parasite infections, namely schistosomiasis, opisthorchiasis, clonorchiasis, strongyloidiasis, malaria, and Chagas disease with human cancers and review mechanisms by which parasites may promote, or impede carcinogenesis (Table 1).
Schistosomiasis and Cancer Schistosomiasis is a neglected disease caused by infection with blood fluke trematodes of the genus Schistosoma. Out of 207 million cases of schistosomiasis currently estimated worldwide, 90% occur in sub-Saharan Africa (Steinmann et al., 2006). Schistosomiasis is considered the most important helminth parasite of humans in terms of morbidity and mortality. The five species of Schistosoma that infect humans are Schistosoma haematobium, S. mansoni, S. japonicum, S. intercalatum, and S. mekongi. Most human infections are due to S. haematobium, S. mansoni, and S. japonicum. Of those, S. haematobium is the most ubiquitous species in Egypt and in sub-Saharan Africa and causes urogenital schistosomiasis (UGS). The prevalence of schistosomiasis is associated with exposure-related factors, in particular with a favourable environment for the imperative intermediate host snails, sub-optimal sanitation infrastructure, and host genetic factors. Adult worms are usually found in human hosts; their interactions with the host and parasite-derived products including their eggs strongly induce carcinogenesis (Brindley et al., 2015). With regard to schistosomiasis at large, clearly UGS i.e. chronic infection with S. haematobium, is carcinogenic and thus classified as a Group 1 carcinogen by the IARC (IARC, 2012). Any carcinogenicity of infection with other schistosomes is far less evident. Liver and colorectal cancers and lymphoid tumors may be associated with chronic schistosomiasis. Nonetheless, infection with S. japonicum is classified by the IARC as Group 2B, i.e. possibly carcinogenic to humans (IARC, 2012; IARC, 1994). Bladder cancer is a common malignancy of the urinary tract with approximately 400,000 new cases and 150,000 deaths occurring annually (Ferlay et al., 2010). Histological types of bladder cancer include urothelial carcinoma, squamous, adenocarcinoma, micropapillary, small cell and plasmacytoid neoplasms. Urothelial carcinomas account for >90% in the developed world, whereas squamous cell carcinoma is seen predominating in UGS endemic regions (Knowles and Hurst, 2015). Further important risk factors for the induction of bladder cancer are host immune responses and host genetic factors (Fig. 1).