Inflammation and cancer

Our plain-English summary of Inflammation and cancer, by M. Murata (Environmental Health and Preventive Medicine, 2018).

The study

• Author: M. Murata
• Journal: Environmental Health and Preventive Medicine
• Published: 2018;23(1):50
• Type of article: Review
• Cited by: 455 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e.g., asbestos, nanomaterials, and inflammatory diseases such as Barrett's esophagus and oral leukoplakia). Interestingly, several of our studies suggested that inflammation-associated DNA damage in cancer stem-like cells leads to cancer development with aggressive clinical features. Reactive oxygen/nitrogen species from inflammation damage not only DNA but also other biomacromolecules, such as proteins and lipids, resulting in their dysfunction. We identified oxidatively damaged proteins in cancer tissues by 2D Oxyblot followed by MALDI-TOF/TOF. As an example, oxidatively damaged transferrin released iron ion, which may mediate Fenton reactions and generate additional reactive oxygen species. Dysfunction of anti-oxidative proteins due to this damage might increase oxidative stress. Such damage in biomacromolecules may form a vicious cycle of oxidative stress, leading to cancer development. Epigenetic alterations such as DNA methylation and microRNA dysregulation play vital roles in carcinogenesis, especially in inflammation-related cancers. We examined epigenetic alterations, DNA methylation and microRNA dysregulation, in Epstein-Barr virus-related nasopharyngeal carcinoma in the endemic area of Southern China and found several differentially methylated tumor suppressor gene candidates by using a next-generation sequencer. Among these candidates, we revealed higher methylation rates of RAS-like estrogen-regulated growth inhibitor (RERG) in biopsy specimens of nasopharyngeal carcinoma more conveniently by using restriction enzyme-based real-time PCR. This result may help to improve cancer screening strategies. We profiled microRNAs of nasopharyngeal carcinoma tissues using microarrays. Quantitative RT-PCR analysis confirmed the concordant downregulation of miR-497 in cancer tissues and plasma, suggesting that plasma miR-497 could be used as a diagnostic biomarker for nasopharyngeal carcinoma. Chronic inflammation promotes genetic and epigenetic aberrations, with various pathogeneses. These changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.

In plain English

This article was a review in which the author summarized earlier research by the author's own group on how long-lasting inflammation may contribute to cancer. It drew mainly on previous studies of infection-linked cancers, such as liver fluke-related bile duct cancer (cholangiocarcinoma) and Epstein-Barr virus-related nasopharyngeal carcinoma. Asbestos was mentioned only briefly, in a list of pro-inflammatory factors the group had studied, citing two earlier papers, one a pilot study of human lung tissues. The review gave no asbestos data and did not discuss mesothelioma or other asbestos-related diseases. It described DNA damage markers (8-oxodG and 8-nitroguanine), damage to proteins, and epigenetic changes that can silence genes. Among the earlier findings reported, RERG gene methylation was significantly higher in nasopharyngeal carcinoma tissue than in normal tissue, with 78% sensitivity and 100% specificity for screening. Plasma miR-497 was lower in nasopharyngeal carcinoma patients than in non-cancerous control patients. The author concluded that chronic inflammation promotes genetic and epigenetic changes that may be useful biomarkers in liquid biopsy (testing of body fluids such as blood) for early detection and prevention of cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of the author's research group's own previous studies on inflammation-related carcinogenesis
• Who was studied: No single study population. The review covered earlier studies by the group on human tissues, patients, cell lines and animal models of cancers linked to infection and inflammation. These were mainly liver fluke-related cholangiocarcinoma (Thailand) and Epstein-Barr virus-related nasopharyngeal carcinoma (Southern China).
• Exposure: Chronic inflammation from infections (liver fluke, Schistosoma haematobium, Helicobacter pylori, human papillomavirus, Epstein-Barr virus) and from pro-inflammatory factors. Asbestos was listed among these factors with citations to two earlier papers, one titled as a pilot study of asbestos contents in human lung tissues. No fiber type, exposure details or asbestos data were given in the review itself.
• Main results:
  • In the group's earlier study of nasopharyngeal carcinoma biopsy specimens, the methylation rate of RERG was significantly higher in cancer tissues than in normal tissues, with 78% sensitivity and 100% specificity to screen for nasopharyngeal carcinoma.
  • In an earlier microRNA study, plasma miR-497 was lower in nasopharyngeal carcinoma patients than in non-cancerous control patients.
  • In earlier work on liver fluke-related cholangiocarcinoma patients, cases staining positive for the stem cell markers CD133 and/or Oct3/4 showed significantly more 8-oxodG than negative cases, and the positive cases had poor prognoses.
  • In liver fluke-infested patients, urinary 8-oxodG levels fell after anti-parasite therapy and were comparable with levels in healthy subjects 1 year after treatment.
  • In liver fluke-related cholangiocarcinoma tissues, iron ion was detected alongside oxidatively damaged transferrin.
• The authors' conclusion: The author concluded that chronic inflammation promotes genetic and epigenetic aberrations, and that these changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, DNA lesions, 8-Nitroguanine, Stomach Cancer, Carcinoma, STEM, Fenton Reaction, Reactive Oxygen Species (ROS).

Related studies

• Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis — S. Kawanishi, S. Ohnishi, et al. (2017)
• Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis — M. Murata, R. Thanan, et al. (2012)
• Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases — A. Shukla, M. Gulumian, et al. (2003)
• Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung — D. Crouzier, S. Follot, et al. (2010)
• The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution — B. Poljšak, R. Fink (2014)
• Beyond foreign-body-induced carcinogenesis: impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression — F. Okada (2007)

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