Infection and Cancer: Revaluation of the Hygiene Hypothesis (original) (raw)
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Infection, immunoregulation, and cancer
As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.
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Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase ou...
Pathogens and Carcinogenesis: A Review
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Cancer is a global health problem associated with genetics and unhealthy lifestyles. Increasingly, pathogenic infections have also been identified as contributors to human cancer initiation and progression. Most pathogens (bacteria, viruses, fungi, and parasites) associated with human cancers are categorized as Group I human carcinogens by the International Agency for Research on Cancer, IARC. These pathogens cause carcinogenesis via three known mechanisms: persistent infection that cause inflammation and DNA damage, initiation of oncogene expression, and immunosuppression activity of the host. In this review, we discuss the carcinogenesis mechanism of ten pathogens, their implications, and some future considerations for better management of the disease. The pathogens and cancers described are Helicobacter pylori (gastric cancer), Epstein-Barr virus (gastric cancer and lymphoma), Hepatitis B and C viruses (liver cancer), Aspergillus spp. (liver cancer), Opisthorchis viverrine (bile ...
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The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a "clean" environment, termed the "hygiene hypothesis," has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, w...
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International Journal of Molecular Sciences, 2020
Cancer is one of the most aggressive and deadly diseases in the world, representing the second leading cause of death. It is a multifactorial disease, in which genetic alterations play a key role, but several environmental factors also contribute to its development and progression. Infections induced by certain viruses, bacteria, fungi and parasites constitute risk factors for cancer, being chronic infection associated to the development of certain types of cancer. On the other hand, susceptibility to infectious diseases is higher in cancer patients. The state of the host immune system plays a crucial role in the susceptibility to both infection and cancer. Importantly, immunosuppressive cancer treatments increase the risk of infection, by decreasing the host defenses. Furthermore, alterations in the host microbiota is also a key factor in the susceptibility to develop cancer. More recently, the identification of a tumor microbiota, in which bacteria establish a symbiotic relationsh...
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Therapeutic Advances in Gastroenterology, 2016
The data from different studies suggest a bacterial role in cancer genesis/progression, often modulating the local immune response. This is particularly so at the mucosal level where the bacterial presence is strong and the immune system is highly reactive. The epithelial surfaces of the body, such as the skin and mucosa, are colonized by a vast number of microorganisms, which represent the so-called normal microbiome. Normally the microbiome does not cause a proinflammatory response because the immune system has developed different strategies for the tolerance of commensal bacteria, but when these mechanisms are impaired or new pathogenic bacteria are introduced into this balanced system, the immune system reacts to the microbiome and can trigger tumor growth in the intestine. In this review, we discuss the potential role of the bacterial microbiome in carcinogenesis, focusing on the direct and indirect immune adaptive mechanisms, that the bacteria can modulate in different ways.
Commensal microorganisms (the microbiota) live on all the surface barriers of our body and are particularly abundant and diverse in the distal gut. The microbiota and its larger host represent a metaorganism in which the cross talk between microbes and host cells is necessary for health, survival, and regulation of physiological functions locally, at the barrier level, and sys-temically. The ancestral molecular and cellular mechanisms stemming from the earliest interactions between prokaryotes and eukaryotes have evolved to mediate microbe-dependent host physiology and tissue homeostasis, including innate and adaptive resistance to infections and tissue damage. Mostly because of its effects on metabolism, cellular proliferation, inflammation, and immunity, the microbiota regulates cancer at the level of predisposing conditions, initiation, genetic instability, susceptibility to host immune response , progression, comorbidity, and response to therapy. Here, we review the mechanisms underlying the interaction of the microbiota with cancer and the evidence suggesting that the microbiota could be targeted to improve therapy while attenuating adverse reactions.
Infection as a causal factor of cancer
2012
By 2030 nearly one in five of all new cases of cancer in the world, and nearly one in six cancer deaths, will occur in Commonwealth member states (Ferley et al., 2010). Projections of the International Agency for Research on Cancer (IARC) indicate that the number of new cases of cancer in the Commonwealth will rise by more than 77 per cent – from 2,263,427 to 4,003,875 – and cancer deaths by more than 81 per cent – from 1,455,050 to 2,592,240 (ibid.). Lowand middle-income member states, particularly those in South Asia, will bear the brunt of this unfolding cancer pandemic where it is estimated that the number of new cancer cases will rise by 72 per cent and cancer deaths by more than 80 per cent (ibid.). Only effective prevention can reduce the incidence of cancer. A first step towards this is an understanding of the factors that predispose to cancer. These factors differ, often quite markedly, between the more and less developed countries and across different geographical regions....
Springer eBooks, 2022
Infectious agents play an aetiologic role in approximately 20% of cancer cases worldwide. At least, more than ten pathogens, including viruses, parasites, and bacteria are known to contribute to oncogenesis either directly via the expression of their protein products or indirectly via chronic inflammation (Table 1). To date, there are seven oncogenic viruses [human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis virus B and C (HBV and HCV), human T-cell lymphoma virus 1 (HTLV-1), Merkel cell polyomavirus (MCPyV), and Kaposi's sarcoma virus (KSVH or HHV8)], one oncogenic bacterium (Helicobacter pylori), and three oncogenic parasites (Schistosoma haematobium, Opithorchis viverrini, and Clonorchis sinensis), identified as cancer-related pathogens. HBV, HCV, HPV, and H. pylori account for approximately 5% of all cancer cases by leading to hepatocellular carcinoma, cervical cancer and stomach cancer, respectively (Vandeven and Nghiem 2014). Pathogens can generally be divided into direct and indirect carcinogens (Figure 1). The direct carcinogenic pathogens HPV, HTLV-1, EBV, MCPyV and KSVH share several similarities. At least a critical portion of the viral genome can generally be detected in each cancer cell resulting in the expression of viral oncogenes that disrupt cell-cycle checkpoints, inhibit apoptosis and contribute to cell immortalisation. In contrast, the indirect carcinogenic pathogens (HBV, HCV, H. pylori, S. haematobium, O. viverrini, and C. sinensis) do not induce expression of oncogenes, but instead their persistent infection leads to a chronic inflammatory state or immunosuppression that limits the antitumour immune surveillance mechanisms. Because persistent infection is a hallmark of oncogenic pathogens, there is a window of opportunity for cancer prevention by treating the pathogen before malignant progression. Viral oncogenic mechanisms generally include: genomic instability, high rates of cell proliferation, resistance to apoptosis, abnormal DNA repair mechanisms, cell polarity changes and interference with telomere shortening, which often coexist with evasion of the antiviral immune response (Morales-Sánchez and Fuentes-Pananá 2014). Viral persistence and/or latency, in which there is no or little production of viral particles are biologically compatible with the carcinogenic process, due to avoiding of cell death while maintaining the infectious agent hidden from the immune system. Viral persistence in the host is achieved by integrating the viral genome into the cell genome or by expressing viral proteins that equally segregate the viral genome into daughter cells during cell partitioning. The net balance between virus and host preserve the integrity of both. Cell transformation is probably not an evolutionary viral strategy, but rather a biological accident that rarely occurs in the virus-host interaction. All virus-associated tumours result from the cooperation of various events, involving more than persistent infection and viral transformation mechanisms.